Method for producing an analytical magazine

ABSTRACT

A method for producing an analytical magazine is proposed. The analytical magazine is designed to receive a plurality of analytical aids in a plurality of chambers. The method comprises the following steps: providing at least one first component of the analytical magazine, wherein the first component comprises a plurality of receptacles; providing a plurality of analytical aids, wherein the analytical aids are connected to one another and preferably oriented with respect to one another by at least one holding element; introducing the analytical aids into the receptacles; and separating the analytical aids from the holding element.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of International Application No.PCT/EP2010/000864, filed on Feb. 12, 2010, which claims the benefit andpriority of European Patent Application Nos. 09153210.1, filed on Feb.19, 2009 and 09168336.7, filed on Aug. 20, 2009. The entire disclosuresof each of the above applications are incorporated herein by reference.

BACKGROUND

The present invention relates to a method for producing an analyticalmagazine which is designed to receive a plurality of analytical aids.The invention furthermore relates to an analytical magazine. Analyticalmagazines of this type are used in medical diagnostics, in particular,in order to qualitatively or quantitatively detect one or more analytesin body fluids. By way of example, said analytes can be metabolites, forexample blood glucose.

In the field of diagnostics it is necessary in many cases to obtainsamples of body fluid, in particular blood samples or samples ofinterstitial fluid, in order to be able to detect constituents therein,in particular specific analytes. Examples of such analytes are bloodglucose, coagulation parameters, triglycerides, lactate or the like. Inaccordance with the detected concentrations, a decision can then betaken about a corresponding treatment, for example.

In the diagnostic methods mentioned, generally one or a plurality ofanalytical aids are used in order to obtain and/or analyze the samplesof body fluid. Thus, the analytical aids can comprise lancets, forexample, that is to say elements which are designed to produce anopening in a subject's skin, through which the body fluid can be drawn.As an example of such lancets, reference may be made to WO 02/36010 A1(see also, US 2004/0034318).

Furthermore, the analytical aids can comprise one or a plurality of testelements with test chemicals which are designed to change specificdetectable properties under the action of the analyte to be detected. Byway of example, said analytes may comprise electrochemically detectableproperties or the changes thereof and/or optically detectableproperties. For such test chemicals, too, reference may be made to theprior art, for example J. Hönes et al., Diabetes Technology &Therapeutics, Volume 10, Supplement 1, 2008, page 10 to page 26.

In addition, integrated test elements are also known which are used bothfor the purpose of producing a sample of body fluid and for the purposeof transporting the sample and, if appropriate, even for the purpose ofqualitative and/or quantitative analysis of said sample. Examples ofsuch analytical aids are so-called microsamplers, in which, by means ofa lancet, a puncture or incision is produced, the sample is taken and istransported to one or a plurality of test fields with the test chemical.Said test fields can be arranged separately from the lancet, but canalso be part of the lancet itself. Systems of this type, which aredescribed for example in US 2004/0193202 A1, US 2008/0249435 A1 or in WO03/009759 A1 (see also U.S. Pat. No. 7,288,073), are particularlyuser-friendly owing to their high degree of integration.

One technical challenge in providing analytical systems and analyticalaids, however, consists in providing them in large quantities undersuitable conditions. Thus, they generally have to be provided in such away that the analytical aids are stored under sterile conditions, forexample by means of corresponding seals. At the same time, however, theseals must not impair the quality of the analytical aids and must notmake it more difficult to use said analytical aids. For this purpose,the analytical aids are generally provided by means of correspondingmagazines, which are also referred to hereinafter as analyticalmagazines. For systems which are intended to carry out for example acapillary blood analysis fully automatically without the subject'sintervention, a multiplicity of lancets and also a multiplicity of testelements, for example each with one or more test chemicals, may bepresent for example in a magazine of this type.

A multiplicity of different analytical magazines are known from theprior art. In principle, it is possible, independently of the type ofanalytical aid, to distinguish between three main types of magazines,namely round magazines (for example in the form of drums and/or disks),linear magazines (for example in the form of stack magazines, zigzagmagazines or the like) and tape magazines, in which the analytical aidsare arranged on a tape or some other form of at least partly flexiblecarrier. These types of magazines can, in principle, also be used, ormodified, in the context of the invention described below. In the priorart, round magazines are described for example in US 2006/0008389, US2007/0292314, US 2006/0184064, US 2003/0212347 or US 2002/0087056.Linear magazines are described for example in U.S. Pat. No. 6,036,924 orUS 2003/0191415. Tape magazines are described for example in US2002/0188224, in US 2008/0103415, in EP 1360935 A1 or in DE 19819407 A1.

Generally, the disadvantage in the case of analytical magazines, inparticular integrated analytical magazines with combined analytical aidswith lancet function and test element function, consists in ensuringfreedom from contamination and sterility. By way of example, onedifficulty is that each set composed of lancet and test element has tobe kept separate from the respective other sets since at least thelancets have to be kept sterile until immediately before they are used.

However, these requirements in turn increase the outlay for theproduction of the analytical magazines. Owing to the different naturesof lancets and test elements, the history of origination thereof isextremely different. Consequently, these elements of the system aregenerally provided in different forms of presentation for the assemblyof the overall analytical magazine. These requirements mean that inpractice analytical magazines generally have to be filled individually.Thus, by way of example, the lancets and the test elements have to beinserted individually into the analytical magazines and/or intoindividual chambers of the analytical magazines, which generallyrequires a high outlay in respect of apparatus. One exception in thisregard is constituted only by tape-based systems, in which theindividual elements can firstly be applied individually to a carriertape and, having been wound up onto said carrier tape, can then beintroduced into a magazine. In any event, however, the individualanalytical aids have to be applied piece by piece, which requires aconsiderable production outlay.

SUMMARY

Therefore, it is an object of the present invention to provide methodsand devices which at least substantially avoid the disadvantages ofknown methods and devices. In particular, the method proposed isintended to enable production of analytical magazines in the case ofwhich the outlay in respect of apparatus and hence the total outlay forthe production of the analytical magazines can be considerably reduced,without the quality of the analytical magazines and/or of the analyticalaids thereby being impaired.

This object is achieved by means of the methods and devices comprisingthe features of the independent claims. Advantageous developments of theinvention, which can be realized individually or in combination, arepresented in the dependent claims. A method for producing an analyticalmagazine and also an analytical magazine are proposed, wherein theanalytical magazine may be producible in particular using a productionmethod according to the invention. Accordingly, with regard to possibleconfigurations of the analytical magazine and individual aspects of theanalytical magazine, reference may be made to the description of themethod, and vice versa.

The analytical magazine is designed to receive a plurality of analyticalaids in a plurality of chambers. Consequently, an analytical magazineshould be understood to mean a device which can be handled as a unit,which can have a common housing, for example, and which can generally beusable in medical technology. In this case, analytical should generallybe understood to mean the possibility of use for the qualitative and/orquantitative detection of at least one analyte and/or the determinationof at least one further measurable property. In this regard, referencemay be made to the above description, for example. In particular,analytical may thus be understood to mean a diagnostic property, that isto say a use for determining at least one property of a body and/or ofpart of a body of a subject. The analytical magazine can accordingly beused in an analytical system which thus becomes an analytical systemaccording to the invention. By way of example, such a system can be ameasuring device by means of which at least one analyte, for example atleast one metabolite, in a body fluid of the subject is detectedqualitatively and/or quantitatively. By way of example, these systemscan be blood glucose measuring devices.

Analytical aids should generally be understood to mean, in the contextof the present invention, aids which can be used supportively in thecase of the analytical functions described above. In particular, theanalytical aids can be medical and/or diagnostic aids, in particularaids which are designed to be used in the case of a qualitative and/orquantitative detection of at least one analyte, for example one or moreof the abovementioned analytes, in a subject's body fluid, for exampleblood, interstitial fluid, urine or similar body fluids. In particular,the analytical aids can be configured as disposable aids (disposables),that is to say be intended for single use. The analytical aids canaccordingly comprise for example at least one lancet, that is to say anelement which is designed to produce at least one opening in thesubject's skin, for example an ear lobe, a finger pad, or a forearm ofthe subject. By way of example, said lancets can comprise one or morepuncturing elements, with needle tips and/or sharpened tips. Othersharp-edged elements can also be used alternatively or additionally, forexample blades, sharp-edged tips or the like. The lancets can beproduced for example from bar-type starting materials, for example inthe form of needle-type lancets. However, the use of one or more lancetsproduced from plate-type materials, in particular metal sheets, isparticularly preferred in the context of the present invention. Thiswill be explained in greater detail below.

As an alternative or in addition to lancets, the analytical aids canalso each comprise one or a plurality of test elements. These testelements have at least one test chemical which is designed to change atleast one measurable property in the presence of at least one analyte tobe detected. Said test chemical, designed to indicate the presenceor—which is intended to be encompassed thereby—the absence of the atleast one analyte by itself or in interaction with the analyte and/orfurther auxiliary materials, can be configured in various ways. In thisregard, reference may for example again be made to the article by J.Hönes et al. cited above. Furthermore, reference may be made to WO2007/012494 A1 (see also, US 2008/0213809), for example, which describesparticularly moisture-stable test chemicals. The test chemicalsmentioned in these documents can also be used, individually or incombination, in the context of the present invention. In particular, itis possible to use strongly specific test chemicals, in the case ofwhich the detection reacts specifically to the at least one analyte. Theat least one measurable property, from the measurement of which the atleast one analyte can be detected qualitatively or quantitatively, cancomprise for example at least one electrochemical property and/or atleast one optical property. By way of example, as is explained ingreater detail below, the test chemical can be embodied in the form ofone or more test fields.

Furthermore, the analytical aids can also be configured in such a waythat they are configured as combined test elements. Thus, by way ofexample, combined test elements with at least one lancet and at leastone test chemical can be used, wherein the test chemical can be designedto change at least one measurable property in the presence of the atleast one analyte to be detected. By way of example, the test elementcan be integrated directly into the lancet. Thus, by way of example, thetest chemical can be taken up at the end of the lancet and/or coverparts of the lancet. Alternatively or additionally, however, it is alsopossible for the lancet and the test element to be formed separately,for example in each case at least one lancet and in each case at leastone test element per chamber of the analytical magazine. These parts ofthe analytical aid may for example also be handled separately, suchthat, by way of example, the lancet can be handled by an actuator of asystem in order to perform a puncturing movement and/or collectingmovement, while the test element for example remains unchanged, forexample within the chamber. Thus, by way of example, the system can bedesigned to carry out a puncturing and/or collecting movement by meansof the at least one lancet and/or a capillary element optionallycontained in the lancet, such that body fluid can be taken up by thelancet directly during a puncturing operation and/or during a samplingmovement. In this case, firstly a puncture into the subject's skin canbe produced, body fluid can be collected and the latter can then betransferred to the test element, for example during a backward movementof the lancet, back into the chamber. Other configurations are alsopossible.

As an alternative or in addition to lancets and/or test elements, theanalytical aids can comprise further elements which are used for ananalysis purpose. Thus, by way of example, transfer elements and/orcollecting elements may be included, which serve the purpose of takingup and/or transporting body fluid. By way of example, such transportelements and/or collecting elements can be used to take up blood and/orinterstitial fluid from the subject's skin and/or a location within thesubject's body and/or a location on the subject's skin and/or to effecttransport to a test element, in particular one or more test fields. Suchtransport can be effected by a transport movement, for example, by meansof one or more transport elements which are configured in movablefashion and can take up and transfer a quantity of the sample of bodyfluid. Alternatively or additionally, other transport elements and/orcollecting elements may also be provided, for example capillaries and/orelements with capillary action. By way of example, closed capillaries orcapillary channels, in particular capillary gaps, may be involved inthis case. Combined analytical aids having at least one lancet functionand at least one capillary function are also referred to hereinafter asmicrosamplers.

As explained above, it is particularly preferred for the analytical aidsto be received in the chambers in such a way that exactly one analyticalaid is received in one chamber. If the analytical aid itself comprisesin each case a plurality of analytical sub-aids, such as, for example,in each case at least one lancet and in each case at least one testelement, then it is possible, by way of example, for the in each case atleast one test element and/or the in each case at least one lancet whichare provided for a single, common test (for example a single taking-upof body fluid and/or analysis of body fluid) to be received in a commonchamber. This configuration, in which one chamber receives respectivelyone analytical aid, for example with in each case at least one sub-aidin the form of a test element and/or with in each case at least onesub-aid in the form of a lancet, can be realized particularly in thecase of a disk-shaped magazine, or else in the case of other designs ofmagazines, such as rod-shaped magazines, for example. As an alternativeto a configuration in which each analytical aid is received in aseparate chamber, a configuration in which a plurality of analyticalaids of identical type or of different types are received in one chamberis also possible. One example of such a configuration is a tape magazinein which a good winding with a plurality of unused analytical aids isreceived in a first chamber and a poor winding with a plurality of usedanalytical aids is received in a second chamber. Other configurationsare also possible.

In this case, a chamber should generally be understood to mean anelement which has at least one at least partly closed cavity in whichthe analytical aid can be received. In this case, the cavity can alsocomprise one or more openings, as will be explained in greater detailbelow. The chambers can also comprise in each case one or moresub-chambers and can comprise in each case one or more chamber wallsfacing an interior of the chambers.

The method for producing the analytical magazine comprises the methodsteps described below. The method steps are preferably, but notnecessarily, carried out in the order presented. Other orders are alsopossible, in principle. Furthermore, the method can comprise additionalmethod steps not described. Furthermore, individual or a plurality ofmethod steps can be carried out repeatedly and/or can be carried outtemporally in parallel and/or in temporally overlapping fashion.

In a first method step, at least one first component of the analyticalmagazine is provided. Said first component can comprise for example acomponent of a housing of the analytical magazine. By way of example,the component can be configured such that it is stiff at least in part.The process of providing can be effected manually and/or automatically,for example. In this case, the first component has a plurality ofreceptacles. By way of example, in each case at least one receptacle canbe provided for each of the abovementioned chambers, said at least onereceptacle being assigned to the respective chamber. Said receptaclescan comprise for example depressions, rails, grooves, slots, webs,walls, projections or similar elements which are able at least in partto fix the analytical aids and/or parts of said analytical aids and/orto prevent, within predetermined limits, a change in the position and/ororientation of said analytical aids. The receptacles can also be part ofthe subsequent chambers, for example in the form of sub-chambers, forexample upwardly open sub-chambers or chambers which are closed off in asubsequent method stage, for example, in particular by means of afurther component, for example by means of a cover. By way of example,the receptacles can comprise depressions which subsequently constitute apart of the walls of the chambers.

In a further method step, a plurality of analytical aids of the typedescribed above are provided. If the analytical aids respectivelyreceived in a chamber consist in each case of different types ofanalytical sub-aids, then these sub-aids can be provided in each case indifferent method steps and/or also be provided jointly with all or somefurther sub-aids. The process of providing can in turn be effected forexample manually or else in wholly or partly automated fashion.

In contrast to the prior art, however, the proposed production method inaccordance with a first aspect of the present invention proposes thatthe analytical aids not be provided and inserted into the magazine pieceby piece, rather that they be provided and inserted into the magazinepreferably all at once. In this case, all the chambers can be loadedsimultaneously with the analytical aids and/or, this being intended tobe equivalent, with sub-aids if the analytical aids are in each casecomposed per se of a plurality of sub-aids. At the very least, aplurality of chambers should be loaded simultaneously with at least onetype of analytical aid and/or a sub-aid, preferably all the chambers.The outlay on assembly can thereby be considerably reduced.

Accordingly, it is proposed that the analytical aids (or, equivalently,the sub-aids) provided be connected to one another and preferablyoriented with respect to one another by at least one holding element.The process of providing can then be effected in this connected andpreferably oriented form. In this case, a holding element shouldgenerally be understood to mean an element which is suitable for jointlyproviding the plurality of analytical aids. Examples of this holdingelement are described in greater detail below. In this case, anorientation of the analytical aids with respect to one another can beunderstood to mean, for example, at least substantial fixing of anabsolute position and/or a spatial orientation (for example an angularorientation) of the analytical aids with respect to one another. In thiscase, slight deviations are also possible, however, which may lie withinthe scope of predetermined tolerances, for example, which may bepredetermined for example by the tolerances of the process of receivingthe analytical aids in the chambers.

In a further method step, the analytical aids or, this being intended tobe equivalent in the context of the present invention, the sub-aids areintroduced into the receptacles. This process of introducing can beeffected for example by simple laying in, inserting or the like and canfor example in turn be effected manually or else in at least partlyautomated fashion. In this case, in a manner corresponding to theprocess of providing the plurality of analytical aids, the process ofintroducing can be effected at least substantially simultaneously for aplurality or preferably all of the chambers, that is to saysubstantially in one method step for all the analytical aids or sub-aidsprovided in the previously described step.

In a further method step, the analytical aids are then separated fromthe holding element. The process of separating can preferably beeffected wholly or partly after and/or during the process of introducingthe sub-aids into the receptacles. In this case, separating during theprocess of introducing should be understood to mean separating duringone or a plurality of method steps that are necessary in order to beable to introduce the sub-aids into the receptacle. The production ofthe sub-aids may substantially be concluded at this point in time, suchthat they may still be connected at this point in time. The separationcan then be effected directly before and/or during these method stepsand/or at a point in time at which the sub-aids have already beenintroduced in part into the receptacle and/or at a point in time atwhich the sub-aids have already been completely introduced into thereceptacle. As an alternative or in addition, however, complete orpartial separation can also be effected during and/or before the processof introducing into the receptacles. In this case, it is possible to usea fixing device, for example, in order to fix the analytical aids and/orsub-aids temporarily after separation before they are introduced intothe receptacles. The process of separation can be effected byconventional separating methods, for example, which may in particularalso be adapted to the manner in which the analytical aids or sub-aidsare connected to the holding element. By way of example, breakingmethods, cutting methods (in particular laser cutting methods and/ormechanical cutting methods), stamping methods, chemical separatingmethods or combinations of the stated and/or other separating methodscan be used for this process of separating, as will be explained in evengreater detail below.

The method proposed has a large number of advantages over known methods.The great simplification of the outlay for production should bementioned as the principal advantage. Thus, by way of example,analytical magazines in which the analytical aids are preferablyarranged separately from one another in different chambers can beproduced with extremely little outlay. The analytical aids may behandled for example wholly or in part independently of one another, thatis to say independently of the analytical aids received in the otherchambers, in contrast for example to analytical aids that are receivedon tapes. Nevertheless, the outlay for loading the individual chamberswith analytical aids can be considerably reduced by the method proposed,since the individual chambers now no longer need to be loadedindividually. Thus, it is now possible for groups of chambers and/or allchambers to be loaded simultaneously. These advantages are achievedwithout accepting disadvantages with regard to losses of quality, sincethe sterility of the individual chambers can be ensured for example bycorresponding seals described in even greater detail below.

The method proposed can be advantageously developed in various ways.Thus, the at least one first component of the analytical magazine ispreferably configured as a substantially rigid component, that is to sayas a component which is not subjected to any significant flexure and/orother deformations at least under the action of its own weight.Accordingly, the above-described receptacles are preferably arranged ina fixedly predetermined alignment and/or orientation with respect to oneanother. Accordingly, as explained above, it is also possible for the atleast one holding element to be configured preferably in substantiallyrigid fashion.

The analytical magazine can, in principle, comprise the plurality ofchambers in any desired arrangement with respect to one another. Thus,by way of example, rod magazines, series magazines, zigzag magazines orthe like are conceivable. In particular, reference may be made to theabovementioned types of magazines. It is particularly preferred for theanalytical magazine to have a disk form, in particular a form of acircular disk and/or an annular disk. Accordingly, the chambers and/orthe receptacles can be arranged in the disk-shaped analytical magazinesubstantially in radial orientation. By way of example, it is possibleto configure the analytical magazine in the form of the circular diskand/or annular disk in such a way that a sampling movement can becarried out by means of the analytical aids and/or by means of at leastone of the analytical aids received in each chamber and/or by means ofat least one sub-aid. A sampling movement may be understood to mean, forexample, a puncturing movement and/or a collecting movement forproducing and/or collecting and/or transferring a sample and/or part ofa sample of body fluid. Accordingly, this sampling movement can beeffected in a radial direction, for example. For this purpose, at leastone opening can be provided for example in the case of the annular diskinside the magazine, for example at least one actuator and/or part of anactuator system of an analytical system engaging into said at least oneopening in order to be able to couple to the analytical aids and/orsub-aids in each chamber (for example successively) and to carry out thesampling movement. For the coupling, reference may be made for exampleto the prior art cited above, for example WO 02/36010 A1 (see also, US2004/0034318). However, other types of coupling are also possible, inprinciple. Exemplary embodiments of circular-disk-shaped and/orannular-disk-shaped magazines are described in greater detail below.

Accordingly, the at least one holding element can also be adapted to theconfiguration of the magazine. Thus, by way of example, in the case of arod-shaped magazine, the holding element can be configured for providingthe analytical aids in a parallel arrangement with respect to oneanother. In the case of a circular-disk-shaped and/or annular analyticalmagazine the holding element can be configured for example for providingthe analytical aids in a radial orientation with respect to one another.By way of example, as explained above, the analytical aids can compriselancets and/or microsamplers as analytical aids and/or sub-aids, whichcan be provided for example by means of the holding element in a radialorientation with respect to one another, that is to say a radiateorientation with respect to one another, for example in an equidistantarrangement. This process of providing can be effected for example insuch a way that the tips of said lancets and/or microsamplers in eachcase point radially outward.

The holding element can, in principle, be constructed comparativelycomplexly and can comprise a multiplicity of sub-elements, for example.Accordingly, the holding element can be configured for a plurality ofloading processes. It is particularly preferred, however, for theholding element to be configured as a disposable holding elementconfigured for exactly one loading process or a limited number ofloading processes. Accordingly, it is particularly preferred for theholding element to be configured comparatively simply, for example as anintegral holding element. In particular, the analytical aids can beworked wholly or in part from a basic material of the holding element.By way of example, this can be a metallic basic material from whichanalytical aids in the form of lancets and/or micro samplers, forexample, are worked in one or a plurality of work steps, thus givingrise to the actual holding element and the analytical aids or partsthereof. For the working process it is possible in this case to use, inprinciple, any desired, for example mechanical and/or chemical methods,for example etching methods and/or cutting methods and/or laser methods.The holding element can comprise at least one simple disk, for example,that is to say a planar, substantially plate-shaped element whoselateral extents exceed its thickness by a multiple. By way of example,the disk-shaped element can comprise a simple metal disk. By way ofexample, said metal disk can be configured as a substantiallyrectangular and/or round metal disk, which is preferred particularly inthe case of the configuration of the analytical magazine as a roundanalytical magazine, in particular with a radial orientation of theanalytical aids. By way of example, the analytical aids can be workedwholly or in part from said disk, such that the analytical aids areformed and the remaining disk forms the holding element or a partthereof.

The analytical aids can be produced in particular integrally with theholding element. This is preferred in particular when the holdingelement is configured as a disposable holding element. In this case, theanalytical aids can be configured completely or in part integrally withthe holding element. If a plurality of sub-aids are provided peranalytical aid, then one, a plurality or all of said sub-aids can beconfigured integrally with the holding element.

The integral configuration can be effected, for example by virtue of thefact that the analytical aids or, this being intended to be equivalent,sub-aids can be worked from a blank element of the holding element inone or a plurality of production steps. Said blank element can forexample in turn comprise a plate-shaped element, in particular adisk-shaped element, for example a metal disk. The process of workingthe analytical aids or sub-aids can be effected for example by knownwork steps, in particular etching processes. Thus, lancets, inparticular, can also be worked from the blank element of the holdingelement for example by means of one or more etching processes. The useof at least one etching process is advantageous for other analyticalaids or sub-aids as well. As an alternative or in addition to etchingprocesses, however, other types of production processes can also beused, in particular for working the analytical aids or sub-aids from theblank elements, for example cutting processes, stamping processes or thelike.

A further, very efficient form of holding elements is a holding elementin the form of a long strip or comprising a long strip, which comprisesa multiplicity of arrangements of analytical aids and/or sub-aids, forexample lancets and/or microsamplers. This permits roll-to-rollprocessing, for example.

As explained above, the process of separating the analytical aids orsub-aids from the holding element can be effected using one or aplurality of corresponding separating methods. As explained above, abreaking method, in particular, is preferred. For this breaking method,but also for other types of separating methods, it is preferred if,prior to separating the analytical aids from the holding element, atleast one connection is provided between the analytical aid and theholding element. Said connection can be adapted to the particular use ofthe at least one separating method. By way of example, said connectioncan comprise at least one bridge and/or at least one other connectingelement, which is preferably likewise configured integrally with theholding element and/or the analytical aids. Said connection canpreferably comprise at least one desired breaking location, particularlywhen at least one breaking method is used. The desired breaking locationcan comprise for example a tapered portion and/or a scribed portionand/or some other type of weakening of a material thickness of theconnecting element. A targeted reduction of the material strength or anembrittlement in the region of the desired breaking location is alsopossible, for example a targeted production of glass hardness in anotherwise tough elastic steel, for example by means of a laser.Preferably, the connection is configured in such a way that after itsseparation or after the analytical aids have been separated from theholding element, substantially no disturbing residues which mightsubsequently impair the function of the analytical aid remain on theanalytical aid, for example the lancet. It can thus be ensured by meansof the abovementioned tapered portions and/or desired breakinglocations, for example, that a clean break arises, such that, by way ofexample, sliding of the lancets and/or of other analytical aids and/orsub-aids for a sampling movement is not impaired. In particular, adesired breaking location can be configured in such a way that it isoffset inward from an edge of the analytical aid, for example into awaist of the analytical aid. This has the advantage that breakingresidues that remain, if appropriate, when the analytical aid isseparated from the holding element, do not impede sliding of theanalytical aid in the chamber.

Generally, it is preferred if the chambers and/or the analytical aidsare configured in such a way that the analytical aids are mounted suchthat they are movable wholly or in part for a sampling movement. In thiscase, the movable mounting can be effected for the analytical aid as awhole or else for just one or a plurality of sub-aids of the analyticalaids, for example one or more lancets, while test elements, for example,can remain fixedly within the chambers and/or at other locations of theanalytical magazine. The movable mounting can be effected for example insuch a way that the analytical aids, as will be explained in evengreater detail below, are fixed completely or in part while theanalytical aids are stored in the chambers of the magazine, whereas thisfixing is released and/or overcome for a sampling movement. The samplingmovement can be effected, as explained above, for example by ananalytical system that interacts with the analytical magazine and/orcomprises the analytical magazine, for example a measuring device,which, by way of example, can have one or a plurality of correspondingactuators. These actuators may be designed to interact with theanalytical aids in the chambers and/or with sub-aids of said analyticalaids and to couple to them, preferably individually. These actuators,which may also comprise parts of the magazine itself, may comprise forexample corresponding coupling elements and/or sampling elements bymeans of which the couplings and/or sampling movements can be carriedout, for example one or more grippers, hooks, plungers, slides orcombinations of the stated and/or other elements. Preferably, thesampling movement and/or the system may be designed in such a way thatthe sampling movement comprises a movement toward the subject's skin, ifappropriate including a puncturing movement in the subject's skin,followed by a movement back, away from the subject's skin. By way ofexample, the movement back may comprise a re-magazining, that is to saya movement during which the at least one analytical aid or sub-aid isonce again received completely or in part in the chamber and/or someother chamber of the analytical magazine. In this way, entirelysatisfactory disposal of the analytical aids from a hygiene standpointcan be ensured.

As explained above, the method can comprise further method steps. Thus,by way of example, the analytical magazine can comprise furthercomponents besides the first component. It is particularly preferred,however, if, apart from the analytical aids and the at least one firstcomponent, a smallest possible number of further components is provided,for example a number of one, two, three or preferably at most fourfurther components. In this way, production of the analytical magazinein the simplest possible manner can be ensured.

The method can comprise, in particular, at least one further methodstep, in which at least one second component is applied. Said secondcomponent can for example in turn be a component of a housing of theanalytical magazine. The second component can be applied to the at leastone first component for example directly or indirectly. Thus, the firstcomponent can be configured for example, as explained above, as a basepart of a housing, whereas the second component is configured forexample as a cover part of the housing, or vice versa. Otherconfigurations are also possible. The second component can be applied tothe first component for example with the interposition of furthercomponents. In this case, the first component and the second componentcan be connected to one another by one or more connections, for exampleforce-locking and/or positively locking and/or cohesive connections.Particular preference is given to cohesive connections, for example inthe form of adhesive-bonding connections and/or welding connections, inparticular by laser welding and/or ultrasonic welding.

In the step of applying the at least one second component, in particularto the first component, the chambers can for example be formed ordeveloped. These chambers may arise for example by virtue of the factthat the abovementioned receptacles in the first component form partialwalls of the chambers, whereas parts of the second component formfurther partial walls of the chambers. The second component, too, canaccordingly comprise for example depressions and/or similar constituentparts of the chambers which subsequently form part of the chambers. Thechambers preferably formed or developed by the process of applying theat least one second component may, after the second component has beenapplied, also still be present in a manner such that they are open inpart, for example with one or a plurality of openings, which will alsobe described in detail below. In particular, during the process ofapplying the at least one second component, the receptacles of the firstcomponent with the analytical aids or sub-aids of the analytical aidsreceived therein can be at least substantially closed off. In this case,a process of at least substantially closing off should be understood tomean a process in which the spatial boundaries of the chambers are atleast substantially defined. As explained above, in this case it ispossible, however, for one or more openings to remain, in particular inthe chamber walls. By way of example, at least one sampling opening canbe provided, for example on a side of the magazine which faces thesubject when the analytical magazine or the analytical system is used,for example an outer circumferential side of a circular-disk-shapedand/or annular magazine. Through these sampling openings, where forexample at least one sampling opening of this type can be provided perchamber, the analytical aids and/or sub-aids can emerge from thechambers, for example in order to carry out the sampling movementsmentioned above. As an alternative or in addition to sampling openings,actuator openings can be provided, for example at least one actuatoropening per chamber. These actuator openings can be configured in orderthat an actuator and/or a part of an actuator, in particular of anactuator of the analytical system, can penetrate completely or in partinto the chambers in order to excite the at least one analytical aid toeffect a sampling movement or in order to carry out a sampling movementby means of said analytical aid or sub-aid. These actuator openings canbe provided for example on an opposite side with respect to the samplingopenings, for example a side of the magazine which is remote from thesubject's skin surface, for example an inner circumference of an annulardisk. As an alternative or in addition, however, the actuator openingscan also be provided at side surfaces of the chambers, depending on thetype of coupling of the actuator to the analytical aids.

As an alternative or in addition to the at least one sampling openingand/or the at least one actuator opening, measurement openings canfurthermore be provided, for example in each case at least onemeasurement opening per chamber. Through these measurement openings, itis possible, for example, to perform measurements on the optional testelements received completely or in part in the chambers, for exampleoptical and/or electrical measurements. By way of example, themeasurement openings can comprise measurement windows, which can beconfigured as open or else closed off with a transparent material, inorder, by way of example, to be able to measure a change in an opticalproperty, for example a color change, on one or more test fields.

As an alternative or in addition to the abovementioned types ofopenings, test element openings can for example also be provided,preferably in turn for example at least one test element opening perchamber. Through these test element openings, one or more test elementscan be introduced completely or in part into the chambers. As describedin greater detail below, this can be effected for example in such a waythat one or more test element fields are applied to said test elementopenings and/or introduced into said test element openings at least inpart from outside in such a way that parts or regions of said testfields face the interior of the chambers. These regions, which are thusreceived inside the chambers, can thus form per se separate sub-aids inthe form of test elements which can be assigned respectively to achamber. This will be described in even greater detail below.

During the process of applying the at least one second component, it ispossible, in particular, to secure the analytical aids in the chambers,in particular the receptacles of the first component, at leastsubstantially against an unintentional change in position, in particularagainst slipping and/or rotating. This can be effected for example by aforce and/or stress being exerted on the aids, which can be ensured forexample by means of corresponding shaping of the first component and/orof the second component. Said force and/or stress and/or deformation maybring about for example a flexing of flexible aids, for example flexiblelancets and/or microsamplers, in particular metal lancets in the form offlat lancets. The stress and/or force can for example be cancelledduring a sampling movement and/or be overcome by the actuator, forexample by the actuator providing a higher force and/or higher stress.

The method according to the invention can furthermore comprise a methodstep in which at least one test chemical is applied. Said test chemicalcan be applied for example to the first component and/or the secondcomponent and/or a third component, not yet mentioned, in particular acarrier. The process of applying the test chemical can be effected forexample after the process of applying the second component, but can, asan alternative or in addition, also be effected in an upstream methodstep and/or simultaneously. As explained above, the test chemical isdesigned to change at least one measurable property in the presence ofat least one analyte to be detected, for example an optically and/orelectrically measurable property. In this regard, reference may be madein particular to the above description.

In this case, the process of applying the test chemical is effected insuch a way that in each case at least one region of the test chemicalfaces the interiors of the chambers. By way of example, in each case oneor a plurality of regions of the test chemical can be assigned to ineach case exactly one chamber. This can be effected, for example, asexplained above, by virtue of the fact that each chamber has, forexample in its chamber wall, at least one test element opening to whichthe test chemical is applied from outside and/or into which the testchemical is introduced at least in part, such that in each case at leastone region faces the interior of the respective chamber. In this way,from the regions of the test chemical which in each case face a chamber,in each case one or a plurality of test fields can arise which can bepart of the analytical aid and which can form, in particular, one or aplurality of sub-aids of the analytical aids. In this case, the regionsof the test chemical which face the interiors of the chambers areintended preferably to be accessible from inside the chambers.

The process of applying the at least one test chemical can be effectedfor example by means of at least one carrier. Thus, by way of example, acarrier in the form of one or more disks and/or films and/or othercomponents and/or structural elements can be provided, to which the testchemical is applied and which is applied in such a way that the testchemical faces the chambers. The carrier can subsequently be removedand/or can also remain wholly or partly a constituent part of theanalytical magazine.

After the test chemical has been applied, it can optionally additionallybe covered, said test chemical being closed off and/or received in theanalytical magazine in moisture-tight fashion, for example. In this way,by way of example, non-moisture-stable test chemicals can also be used.Particularly if moisture-stable test chemicals are used, however, such acovering of the test chemical can also be completely dispensed with.

It is possible to realize analytical magazines in which the chamberscomprise analytical aids with at least one lancet and at least one testelement in the form of at least one test field, for example. Thus, byway of example, by means of the at least one lancet and/or a collectingelement or transfer element during a sampling movement, a sample of thebody fluid can be produced and/or taken up and transferred inside thechamber. This transfer can be effected, as explained above, for exampleby means of a movement back as part of the sampling movement, wherein apart of the sample that has been taken up for example on the lancetand/or the collecting element and/or the transfer element is transferredinside the chamber. As an alternative or in addition, the taking upand/or the transfer, as explained above, can also be effected forexample by a capillary action of at least one capillary element of theanalytical aid, which performs a transfer inside the chamber currentlybeing used in each case. The transfer can be configured, in particular,in such a way that during said transfer, the sample that has been takenup is transferred completely or partly to the at least one test element,in particular to one or more test fields, for example theabove-described at least one test field produced by the process ofapplying the test chemical. For this purpose, the analytical systemusing the analytical magazine can also additionally comprise one or moreactuators designed to support the transfer of the sample from theanalytical aid, for example a lancet and/or a microsampler, to the atleast one test element, for example a test field. By way of example, anactuator can be provided which engages into the chamber and presses asample-laden lancet and/or a microsampler onto a test field.

The above-described method variant or variant of the test elementmagazine in which the test chemical is configured in such a way that atleast one region of the test chemical faces the interiors of thechamber, in particular in the form of one or a plurality of test fieldsper chamber, can be carried out in particular in such a way that thetest chemical is applied jointly for a plurality, preferably for all, ofthe chambers. Thus, by way of example, the at least one test chemicalcan be applied in the form of one or more test chemical fields, inparticular in the form of one or more continuous test chemical fields.In this case, a test chemical field should be understood to mean an areacoated with test chemical throughout or not throughout, which area canalso comprise a plurality of non-contiguous sub-areas. This common testchemical field which is provided jointly for a plurality or preferablyall of the chambers can be embodied for example in the form of arectangular field, round field or field shaped in any desired manner, inprinciple. This test chemical field can be applied for example on thecarrier described above, for example a carrier film and/or some otherstructural element. The carrier can comprise for example a plasticmaterial, for example a plastic film, and/or a paper material and/or aceramic material and/or a metallic material, or a combination of thestated and/or other materials. In particular, a continuous andpreferably integral carrier can be used in this case.

In particular, the test chemical field, this being preferredparticularly for round analytical magazines, can be configured in roundor annular fashion. Thus, by way of example, at least one chemical ringcan be provided which has an annular carrier, preferably a continuousand in particular integral carrier (for example a carrier ring), andalso at least one test chemical field applied thereto, preferably acontinuous test chemical field. As an alternative, however, provisionmay for example also be made of a differently designed test chemicaldisk and/or a test chemical tape, with a correspondingly designedcarrier, preferably a continuous and/or integral carrier, and at leastone test chemical field applied thereto. Other configurations are alsopossible, however, which can be adapted to the respective form of theanalytical magazine. The test chemical field is intended to provide theregions of the test chemical for a plurality of chambers, preferably forall of the chambers simultaneously, in particular the test fields forthe respective chambers. If a plurality of test fields with differenttest chemicals are provided per chamber, then it is possible, by way ofexample, for each type of test chemical, to provide or apply a separatetest chemical field for a plurality or preferably all of the chambers.These different types of test chemical fields can be provided onseparate carriers or else on common carriers. Preferably, a commoncarrier, in particular an integral carrier, is also provided in the caseof a plurality of test chemical fields and/or a plurality of types oftest chemical fields. In particular, the carrier can also be coveredwith the test chemical throughout, that is to say in such a way that thetest chemical field is not interrupted for the individual chambers, butrather is formed integrally for the plurality of chambers, preferablyfor all of the chambers. As an alternative, however, it is also possibleto use a carrier coated with test chemical not throughout. The carrieritself is preferably configured integrally itself, however, for exampleas an integral carrier ring.

As explained above, the method can comprise further method steps, inparticular method steps in which the chambers are sealed completely orin part, individually, in groups or all together. For this purpose, inat least one further method step, at least one seal can be applied to atleast one opening of the chambers. If a plurality of openings areprovided per chamber, for example the openings mentioned above, thenthese can be closed off, or sealed, individually or in groups orjointly. In this case, the seal can for example also be applied in sucha way that sealing is effected for each type of openings for a pluralityor preferably all of the chambers simultaneously. In this case, sealingshould generally be understood to mean a process of closing off theopenings which, at least in the context of customary use durations orstorage durations for the analytical magazine, at least substantiallyprevents ingress of ambient influences, in particular air humidityand/or germs, inside the chambers. In this way, by way of example, it ispossible to ensure a constant quality of the analytical aids over apredetermined storage duration, for example a storage duration of a fewmonths up to a few years.

The sealing can be effected for example by at least one sealing element,which is preferably configured in such a way that it does not impair therespective function or purpose of use of the respective at least oneopening. By way of example, it is possible to configure the sealing inthe case of the at least one sampling opening in such a way that thelatter can be opened for the sampling movement by the analytical aidand/or a further element of the analytical magazine and/or of theanalytical system, for example by piercing and/or by cutting.Accordingly, by way of example, the at least one actuator opening can beconfigured such that it is opened for an actuator movement in thecontext of the sampling movement, for example by the actuator itselfand/or a further element of the analytical magazine and/or of theanalytical system. If at least one measurement opening is provided, thenthe sealing of this measurement opening can be configured for example insuch a way that the measurement opening is uncovered for a measurement.As an alternative or in addition, depending on the type of measurement,the sealing can also be configured for example in such a way that itenables an optical measurement, for example, for which purpose thesealing of the at least one measurement opening can be configured forexample as transparent to detection light and/or excitation light.

The at least one optional test element opening can adopt a special role.This test element opening can be closed off and/or sealed for example asearly as during the process of applying or by the process of applyingthe test chemical in accordance with the description above. In addition,at least one seal can be applied to this at least one test elementopening, for example in order to seal remaining interspaces.

The seal can comprise one or more sealing elements, which can be adaptedto the purposes described above and which can also be formed integrallyfor a plurality of openings. By way of example, corresponding sealingfilms can be provided, for example thin plastic films and/or metalfilms. Sealing elements of this type are known, in principle, from theprior art.

As explained above, an analytical magazine is furthermore proposedbesides the proposed method in one or more of the method variantsdescribed. This analytical magazine may be producible for exampleaccording to a method in accordance with one or more of the methodvariants described, although other production methods can also be used,in principle. This analytical magazine comprises a plurality ofanalytical aids received in chambers. The analytical magazinefurthermore comprises at least one test chemical which is designed tochange at least one measurable property in the presence of at least oneanalyte to be detected.

Furthermore, it is proposed to realize the above-described aspect ofjointly applying the test chemical for a plurality of chambers,preferably for all of the chambers, also if appropriate independently ofthe production method mentioned. Accordingly, the at least one testchemical can be applied to a continuous carrier and form at least intest chemical field within the meaning of the definition above. Inparticular, the at least one test chemical field and the continuouscarrier can form at least one chemical ring and/or at least one testchemical tape. In this regard, reference may be made to the descriptionabove.

In this case, the test chemical field is applied to a continuouscarrier. In this case, a continuous carrier should be understood to meana carrier which carries test chemical for a plurality and preferably forall of the chambers simultaneously. In particular, the carrier can beconfigured in integral fashion, for example as a carrier ring. Withregard to the possible configurations of the carrier, reference may bemade for example to the above description of the method. This at leastone test chemical field, which, as explained above, can have one or elsea plurality of sub-fields, including non-contiguous sub-fields, hereprovides in each case at least one region of the test chemical field tothe chambers, this in each case at least one region of the test chemicalfield facing the interiors of the chambers. As explained above, this atleast one region can therefore produce in particular per chamber in eachcase at least one test field which forms a part of the analytical aidsreceived in the chambers and/or of the sub-aids of said analytical aids.

The test chemical field can be in particular part of a housing of theanalytical magazine, in particular part of an outer magazine housingwall. By way of example, as explained above, this can be effected byvirtue of the fact that the test chemical field is applied to an openingof a housing part of the housing from outside, such that the testchemical field is accessible at least partly from inside the chamber. Byway of example, as explained above, the housing can be formed insubstantially rigid fashion, that is to say in such a way that itsubstantially does not change its form at least under the action of theforces resulting from its own weight. The housing can comprise forexample the abovementioned components, that is to say the at least onefirst component, the optionally at least second component and, ifappropriate, one or more further components. The housing can comprisefor example one or more plastic materials and/or one or more ceramicmaterials and/or one or more further materials, for examplethermoplastic materials, thermosetting plastic materials, if appropriatewith corresponding fillers or combinations of the stated and/or othermaterials.

The described method and/or the described analytical magazine in one ormore of the embodiments described has, as already indicated above,numerous advantages over known methods and devices. In particular, theanalytical magazine can be used for so-called microsamplers, that is tosay analytical systems in which the sample production and the samplingand optionally also the sample analysis are effected within a singleintegrated system. Preferably, it is possible in this case to take upsmall sample volumes, for example sample volumes of less than 1 μl, inparticular less than 500 μl.

The production process can be substantially restricted to the handlingof a small number of structural elements. In a first method step, by wayof example, in accordance with one of the method variants describedabove, structures of individual lancets, for example needle elements,can be etched, for example from a metal sheet. In this way, it ispossible for example to produce a metal disk comprising the holdingelement and the lancets. The individual lancets can be interconnected bymeans of the metal disk. The metal sheet can subsequently for example belaid into the first component, for example a plastic component of ahousing produced completely or partly from plastic, and/or be laid ontothe latter. During the subsequent separation of the lancets, the latterpreferably directly in ordered fashion are deposited all at once intothe chambers of the housing, preferably without separate orientation ofthe lancets being necessary for this purpose. In this way, by way ofexample, it is possible to dispense with handling of individual, inparticular miniaturized, disposables during insertion into therespective magazine chambers. In a next step, the housing can becompleted by a further housing part, the now separated lancets beingheld in their chambers, for example. Afterward, as explained above, themagazine housing can be covered with a chemical ring, for example, whichpreferably has a test chemical field throughout. Overall, the productioncosts and the outlay for production can be considerably reduced in thisway.

Furthermore, by means of the method proposed, it is also possible toreliably prevent cross-contamination of the analytical aids within thechambers. By way of example, this can be achieved by one or more of theabove-described connection methods by means of which a plurality ofhousing parts, for example the first component and the second component,are connected to one another, in which case, in particular, theindividual chambers can be separated from one another. This can beeffected by a laser welding method, in particular, wherein preferablyadjacent chambers are separated from one another by continuous weldingseams.

In particular the integral production of the analytical aids with theholding element or of sub-aids with the holding element has numerousadvantages. Thus, by way of example, it is possible to use specificetching structures for the lancets and/or microsamplers, by means ofwhich the lancets can be connected to the holding element, for example ametal sheet and/or metal frame. By way of example, as explained above,said etching structures can have desired breaking locations and/ortapered portions, such that, by way of example, when the individuallancets are broken out and/or separated in some other way from theholding element, there are no residual break-off residues that mightimpede sliding of the lancets within the chambers. A high processreliability can be ensured in this way.

As a result of the preferred rigid configuration of the test elementmagazine and/or the preferred process of jointly introducing theanalytical aids into a plurality, preferably all, of the chambers bymeans of a corresponding holding element, it is also possible to achieveadvantages for example over analytical aids connected by a tape orsimilar flexible elements and over the production of correspondinganalytical magazines. Handling of tapes is not necessary in this case.Nevertheless, the rigid configuration is not absolutely necessary,however, since, by way of example, the magazine and/or the firstcomponent and/or the holding element can also be configured wholly or inpart in flexible fashion, for example in the form of films, tapes,chains, or the like.

A second aspect of the present invention proposes an analytical magazinewhich, by way of example, but not necessarily, is producible accordingto the above-described method according to the invention. Therefore, forpossible configurations of the analytical magazine described below,reference may be made to the above description of the method or of theanalytical magazine producible by means of the method. However, otherways of producing the analytical magazine are also conceivable. Inparticular, the analytical magazine can also be produced in a differentmanner than by using a holding element for introducing the analyticalaids. Furthermore, the analytical magazine can also be configured in adifferent manner than with a continuous test chemical, that is to sayfor example with separate test chemicals for each individual chamber.However, a common continuous test chemical field in which in each caseat least one region faces a respective chamber, for example in the formof a test chemical ring, is particularly preferred in the context of thesecond aspect of the present invention as well. Furthermore, theabove-described preferred configurations of the first aspect of theinvention, as are in particular also presented in the dependent claims,can also be realized in the context of the second aspect of theinvention as well, including independently of the other features of thefirst aspect of the invention.

The analytical magazine in accordance with the second aspect of theinvention comprises a plurality of analytical aids. The analyticalmagazine has at least two chambers in which the analytical aids can bereceived. In this case, the analytical aids are received in at least oneof the chambers. In this case, basically two principles for receiving inthe chambers are conceivable. Thus, by way of example, in each case oneanalytical aid can be received per chamber, in particular an analyticalaid which comprises at least one sub-aid in the form of a test elementwith a test chemical. Optionally, at least one further sub-aid in theform of a lancet and/or a microsampler can be provided, preferably inaddition, per chamber. In the case of this principle, it is possible forthe analytical aids to be remagazined in particular after use in thesame chamber. As an alternative, however, remagazining in a differentchamber is also possible. This first principle is preferred particularlyin the case of disk-shaped or rod-shaped magazines. According to afurther principle, at least one first chamber for unused analytical aidsand at least one second chamber for used analytical aids can beprovided. In this case, by way of example, the analytical aids can beremoved from the first chamber for a use and be transferred into thesecond chamber after the use, which second chamber can be formed suchthat it is spatially separated from the first chamber. This principlecan be used for example for tape magazines, wherein, by way of example,a good winding for receiving unused analytical aids is provided in afirst chamber and a poor winding for receiving used analytical aids isprovided in a second chamber.

The analytical aids comprise in each case at least one test element withat least one test chemical for detecting at least one analyte in aliquid sample, in particular a body fluid. In this case, the analyticalaids are often also referred to as “tests”, independently of thefunction and configuration thereof. In this case, therefore, a test cangenerally be understood to mean at least an analytical aid which can beutilized for a test process. By way of example, a test element or alancet or else a pair comprising a test element and a lancet may beinvolved in this case, preferably exactly one test being mounted inexactly one chamber. A test can therefore comprise a plurality ofassociated sub-aids, for example. A test can be received in exactly onechamber, for example. In the context of the present invention, however,here and hereinafter no further distinction is made linguistically andin terms of contents between a test and an analytical aid, including thepossibility that a test may comprise a plurality of sub-aids, forexample in each case a test element and a lancet.

In conventional analytical magazines and test elements, in particularfor detecting glucose, generally use is made of a test chemical which issensitive to air humidity and whose function may deteriorate or even belost entirely in the event of excessively long exposure to air.Accordingly, by way of example, conventional test strips have to bestored in containers that are moisture-tight with respect to airhumidity. These containers are usually partly filled with a dryingagent, that is to say a moisture-absorbing material, for exampleactivated carbon. If, in the case of integrated systems, analyticalmagazines and/or analytical aids, for example disposable aids(disposables), are then developed in which test elements are packagedindividually or in groups, these packagings also have to be mademoisture-tight. However, this requirement for moisture-tightnessextremely limits the choice of potential materials, in particularpotential materials for the housing. This is owing to the fact thatadditional requirements may exist which have to be met at the same time.Thus, in most cases, the materials used have to be sterilizable, inparticular by means of ionizing radiation. As an alternative or inaddition, the materials used are generally not permitted to outgas, inparticular not after or during exposure to radiation as a result of asterilization process. Once again as an alternative or in addition, thematerials used have to be suitable for the chosen production process,for example for an injection-molding method and/or some other shapingprocess. Once again as an alternative or in addition, the materials usedshould preferably be biocompatible and/or should be joinable and/orsealable. Further requirements may exist. In this case, in particularthe requirement of moisture-tightness is a requirement that is difficultto satisfy in practice since most plastics are open to moisture inrespect of diffusion, particularly in the case of small wallthicknesses, for example wall thicknesses of less than one millimeter.

According to the invention, therefore, the second aspect of the presentinvention proposes configuring the test chemical in this case in such away that the latter is at least substantially stable with respect toambient influences, in particular with respect to moisture. The testchemical can be present in particular as a dry chemical, in particularon a test strip. In the context of the present invention, a testchemical which is substantially stable with respect to ambientinfluences is understood to mean a test chemical which is stable withrespect to air humidity and advantageously likewise with respect tosterilization methods, in particular sterilization methods usingionizing radiation. In this case, stable is the designation used if,during storage at 32° C. and a relative air humidity of 85% at standardpressure over a time duration of three weeks, the activity, for examplethe enzyme activity of the test chemical of the analytical aid,decreases by less than 50%, preferably by less than 30%, andparticularly preferably by less than 20%. In this case, the activity canbe determined in principle by means of any desired method known from theprior art since, in the context of the definition indicated, only aratio of the decrease in the activity measured by this method to anactivity measured by this method before storage or directly after theproduction of the analytical aid is of relevance. In this case, theactivity can relate in particular to an enzyme activity of a drychemical, in particular in a test strip. By way of example, methods areknown which, for measuring the enzyme activity, extract the enzyme fromthe test chemical or the test strip and subsequently determine theactivity by means of ultraviolet absorption, for example. In thisregard, reference may be made for example to H. U. Bergmeyer: Methodender enzymatischen Analyse [Methods of enzymatic analysis], VerlagChemie, 2^(nd) edition 1970, page 417, or Banauch et al.: A glucosedehydrogenase for the determination of glucose concentrations in bodyfluids, Z. Klin. Chem. Klin. Biochem. 1975 March; 13(3): 101-7. By wayof example, for the test, a test strip with the test chemical can beproduced, the enzyme activity of an enzyme of the test chemical can bemeasured by means of a conventional method, then the above-describedstorage can be carried out and afterwards the same method for measuringthe enzyme activity can be carried out again. This procedure is usuallycarried out with a representative collective of test strips or testchemicals. As an alternative or in addition to stability with respect toambient influences in the form of air humidity, there may preferablyalso be high stability of the test chemical with respect to ambientinfluences in the form of radiation usually used for sterilizing theanalytical aids and/or the analytical magazines overall, for examplegamma radiation and/or beta radiation and/or some other type of ionizingradiation.

As an example of such a test chemical which is stable with respect toambient influences, reference may be made to WO 2007/012494 A1 (see alsoUS 2008/213809), already cited above. The test chemical presentedtherein can also be used in the context of the present invention, byitself or else in combination with one or more other test chemicals. Asan alternative or in addition, the test chemical can also be configuredin the manner described in EP 2093284 A1 or WO 2009/103540 (see also US2011/0143416).

Thus, the test chemical can contain for example an enzyme and a stablecoenzyme, which are stored together. It has surprisingly been found thatlong-term stabilization of several weeks or months at high relativemoisture or even in liquid phase and at elevated temperatures ispossible with the aid of a stable coenzyme. This perception issurprising because it is known that although enzymes have an increasedshort-term stability for some hours in the presence of native coenzyme,they show a lower stability over a longer period. Compared with theseperceptions in relation to the prior art, it was surprising that anenzyme has a distinctly increased long-term stability in the presence ofa stable coenzyme than does an enzyme in the presence of a nativecoenzyme, especially since the stable coenzymes have a lower bindingconstant with the enzyme than does the native coenzyme.

The enzyme stabilized by the method according to the invention may be inparticular a coenzyme-dependent enzyme. Examples of suitable enzymes aredehydrogenases selected from a glucose dehydrogenase (E.C.1.1.1.47),lactate dehydrogenase (E.C.1.1.1.27, 1.1.1.28), malate dehydrogenase(E.C.1.1.1.37), glycerol dehydrogenase (E.C.1.1.1.6), alcoholdehydrogenase (E.C.1.1.1.1), alpha-hydroxybutyrate dehydrogenase,sorbitol dehydrogenase or amino-acid dehydrogenase, e.g. L-amino-aciddehydrogenase (E.C.1.4.1.5). Further suitable enzymes are oxidases suchas, for instance, glucose oxidase (E.C.1.1.3.4) or cholesterol oxidase(E.C.1.1.3.6) and amino transferases such as, for example, aspartate oralanine amino transferase, 5′-nucleotidase or creatine kinase. Theenzyme is preferably glucose dehydrogenase.

It has proved to be particularly preferable to employ a mutated glucosedehydrogenase. The term “mutant” as used in the context of the presentapplication refers to a genetically modified variant of a native enzymewhich, while the number of amino acids is the same, has an amino acidsequence which is modified compared with the wild-type enzyme, i.e.differs in at least one amino acid from the wild-type enzyme. Theintroduction of the mutation(s) can take place site-specifically ornon-site-specifically, preferably site-specifically by using recombinantmethods known in the specialist sector, with at least one amino acidexchange within the amino acid sequence of the native enzyme resulting,appropriate for the particular requirements and conditions. The mutantparticularly preferably has an increased thermal or hydrolytic stabilitycompared with the wild-type enzyme.

The mutated glucose dehydrogenase can in principle comprise the aminoacid(s) which is (are) modified by comparison with the correspondingwild-type glucose dehydrogenase at any position in its amino acidsequence. The mutated glucose dehydrogenase preferably includes amutation at at least one of positions 96, 170 and 252 of the amino acidsequence of the wild-type glucose dehydrogenase, with particularpreference for mutants with mutations at position 96 and position 170,and mutations at position 170 and position 252. It has provedadvantageous for the mutated glucose dehydrogenase to comprise nofurther mutations besides these mutations.

The mutation at positions 96, 170 and 252 can in principle include anyamino acid exchange which leads to a stabilization, e.g. an increase inthe thermal or hydrolytic stability, of the wild-type enzyme. Themutation at position 96 preferably includes an amino acid exchange ofglutamic acid for glycine, whereas in relation to position 170 an aminoacid exchange of glutamic acid for arginine or lysine, in particular anamino acid exchange of glutamic acid for lysine, is preferred. Inrelation to the mutation at position 252, this preferably includes anamino acid exchange of lysine for leucine.

The mutated glucose dehydrogenase can be obtained by mutation of awild-type glucose dehydrogenase derived from any biological source,where the term “biological source” includes in the context of thisinvention both prokaryotes such as, for example, bacteria, andeukaryotes such as, for example, mammals and other animals. Thewild-type glucose dehydrogenase is preferably derived from a bacterium,with particular preference for a glucose dehydrogenase from Bacillusmegaterium, Bacillus subtilis or Bacillus thuringiensis, especially fromBacillus subtilis.

In a particularly preferred embodiment of the present invention, themutated glucose dehydrogenase is a glucose dehydrogenase obtained bymutation of wild-type glucose dehydrogenase from Bacillus subtilis,which has the amino acid sequence depicted in SEQ ID No.: 1(GlucDH_E96G_E170K) or that depicted in SEQ ID No.: 2(GlucDH_E170K_K252L).

The stable coenzyme is preferably a coenzyme which has been chemicallymodified by comparison with the native coenzyme and which has a higherstability than the native coenzyme (e.g. hydrolytic stability). Thestable coenzyme is preferably stable to hydrolysis under testconditions. Compared with the native coenzyme, the stable coenzyme mayhave a reduced binding constant for the enzyme, for example a bindingconstant reduced by a factor of 2 or more.

Preferred examples of stable coenzymes are stable derivatives ofnicotinamide adenine dinucleotide (NAD/NADH) or nicotinamide adeninedinucleotide phosphate (NADP/NADPH), or truncated NAD derivatives, e.g.without the AMP moiety or with non-nucleoside residues, e.g. hydrophobicresidues. Likewise preferred as stable coenzyme in the context of thepresent invention is the compound of the formula (I)

Preferred stable derivatives of NAD/NADH and NADP/NADPH are described inthe aforementioned references, the disclosure of which is herebyexpressly incorporated by reference. Particularly preferred stabilizedcoenzymes are described in WO 2007/012494 (see also, US 2008/213809) andU.S. Pat. No. 7,553,615, the disclosure of which is hereby expresslyincorporated by reference. The stable coenzyme is particularlypreferably selected from compounds having the general formula (II)

with

-   A=adenine or an analog thereof,-   T=in each case independently O, S,-   U=in each case independently OH, SH, BH₃ ⁻, BCNH₂ ⁻,-   V=in each case independently OH or a phosphate group, or two groups    forming a cyclic phosphate group;-   W═COOR, CON(R)₂, COR, CSN(R)₂ with R=in each case independently H or    C₁-C₂-alkyl,-   X¹, X²=in each case independently O, CH₂, CHCH₃, C(CH₃)₂, NH, NCH₃,-   Y═NH, S, O, CH₂,-   Z=a linear or cyclic organic radical, with the proviso that Z and    the pyridine residue are not linked by a glycosidic linkage, or a    salt or, where appropriate, a reduced form thereof.

Z in the compounds of the formula (II) is preferably a linear radicalhaving 4-6 C atoms, preferably 4 C atoms, in which 1 or 2 C atoms areoptionally replaced by one or more heteroatoms selected from O, S and N,or a radical including a cyclic group which has 5 or 6 C atoms and whichoptionally comprises a heteroatom selected from O, S and N andoptionally one or more substituents, and a radical CR⁴ ₂, where CR⁴ ₂ isbonded to the cyclic group and to X², with R⁴=in each case independentlyH, F, Cl, CH₃.

Z is particularly preferably a saturated or unsaturated carbocyclic orheterocyclic 5-membered ring, in particular a compound of the generalformula (III)

where a single or double bond may be present between R^(5′) and R^(5″),with

-   R⁴=in each case independently H, F, Cl, CH₃,-   R⁵═CR⁴ ₂,-   where R^(5′)═O, S, NH, NC₁-C₂-alkyl, CR⁴ ₂, CHOH, CHOCH₃, and-   R^(5″)═CR⁴ ₂, CHOH, CHOCH₃ if there is a single bond between R^(5′)    and R^(5″), and-   where R^(5′)═R^(5″)═CR⁴ if there is a double bond between R^(5′) and    R^(5″), and-   R⁶, R^(6′)=in each case independently CH or CCH₃.

In a preferred embodiment, the compounds according to the inventioncomprise adenine or adenine analogs such as, for example, C₈- andN₆-substituted adenine, deaza variants such as 7-deaza, aza variantssuch as 8-aza or combinations such as 7-deaza or 8-aza or carbocyclicanalogs such as formycin, it being possible for the 7-deaza variants tobe substituted in position 7 by halogen, C₁-C₆-alkynyl, -alkenyl or-alkyl.

In a further preferred embodiment, the compounds comprise adenosineanalogs which, instead of ribose, comprise for example2-methoxydeoxyribose, 2′-fluorodeoxyribose, hexitol, altritol orpolycyclic analogs such as bicyclo-, LNA- and tricyclo-sugars.

It is possible in particular in the compounds of the formula (II) alsofor (di)phosphate oxygens to be replaced isotronically, such as, forexample, O⁻ by S⁻ or BH₃ ⁻, O by NH, NCH₃ or CH₂ and ═O by ═S.

W in the compounds of the formula (II) according to the invention ispreferably CONH₂ or COCH₃.

R⁵ in the groups of the formula (III) is preferably CH₂. It is furtherpreferred for R^(5′) to be selected from CH₂, CHOH and NH. In aparticularly preferred embodiment, R^(5′) and R^(5″) are each CHOH. Inyet a further preferred embodiment, R^(5′) is NH and R^(5″) is CH₂.

In the most preferred embodiment, the stable coenzyme is carbaNAD.

The preferred test chemical is configured in particular for long-termstabilization of the enzymes contained in it. This means that the enzymestabilized with a stable coenzyme is stored, e.g. as dry substance, forexample over a period of at least two weeks, preferably of at least fourweeks and particularly preferably of at least eight weeks, and in thiscase the enzyme activity declines preferably by less than 50%,particularly preferably less than 30% and most preferably by less than20% in relation to the initial enzyme activity.

The test chemical can further be configured for storage of the enzymestabilized with a stable coenzyme at elevated temperatures, for exampleat a temperature of at least 20° C., preferably of at least 25° C., andparticularly preferably of at least 30° C. The enzyme activity in thiscase declines preferably by less than 50%, particularly preferably lessthan 30% and most preferably less than 20% in relation to its initiallevel.

It is possible by the stabilization according to the invention for theenzyme stabilized with a stable coenzyme to be stored even without adrying reagent for a long time, as indicated above, and/or at hightemperatures, as indicated above. It is further possible for thestabilized enzyme also to be stored at a high relative air humidity,e.g. a relative air humidity of at least 50%, in which case the enzymeactivity declines preferably by less than 50%, particularly preferablyless than 30% and most preferably less than 20% in relation to theinitial level.

The storage of the enzyme stabilized with a stable coenzyme can takeplace on the one hand as dry substance and on the other hand in liquidphase. The storage of the stabilized enzyme preferably takes place on orin a test element suitable for determining an analyte. The enzymestabilized with a stable coenzyme is in this case a constituent of thepreferred test chemical which may where appropriate also comprisefurther constituents such as, for example, salts, buffers, etc. The testchemical is in this case preferably free of a mediator.

The enzyme stabilized with a stable coenzyme can generally be employedfor detecting analytes, for example parameters in body fluids such as,for instance, blood, serum, plasma or urine, or in sewage samples orfood products.

Analytes which can be determined are any biological or chemicalsubstances which can be detected by a redox reaction, e.g. substanceswhich are substrates of a coenzyme-dependent enzyme or are themselvescoenzyme-dependent enzymes. Preferred examples of analytes are glucose,lactic acid, malic acid, glycerol, alcohol, cholesterol, triglycerides,ascorbic acid, cysteine, glutathione, peptides, urea, ammonium,salicylate, pyruvate, 5′-nucleotidase, creatine kinase (CK), lactatedehydrogenase (LDH), carbon dioxide etc. The analyte is preferablyglucose. The detection of glucose with the aid of glucose dehydrogenase(GlucDH) is particularly preferred in this connection.

The alteration in the stable coenzyme by reaction with the analyte canin principle be detected in any way. It is possible in principle toemploy here all methods known from the prior art for detecting enzymaticreactions. However, the alteration in the coenzyme is preferablydetected by optical methods. Optical detection methods include forexample the measurement of absorption, fluorescence, circular dichroism(CD), optical rotatory dispersion (ORD), refractometry etc.

An optical detection method which is preferably used in the context ofthe present application is photometry. Photometric measurement of analteration in the coenzyme as a result of reaction with the analyterequires, however, the additional presence of at least one mediatorwhich increases the reactivity of the reduced coenzyme and makes itpossible for electrons to be transferred to a suitable optical indicatoror an optical indicator system.

Mediators suitable for the purposes of the present invention are interalia nitrosoanilines such as, for example,[(4-nitrosophenyl)imino]dimethanol hydrochloride, quinones such as, forexample, phenanthrenequinones, phenanthrolinequinones orbenzo[h]quinolinequinones, phenazines such as, for example,1-(3-carboxypropoxy)-5-ethylphenazinium trifluoromethanesulfonate,or/and diaphorase (EC 1.6.99.2). Preferred examples ofphenanthrolinequinones include 1,10-phenanthroline-5,6-quinones,1,7-phenanthroline-5,6-quinones, 4,7-phenanthroline-5,6-quinones, andthe N-alkylated and N,N′-dialkylated salts thereof, with preference ascounterion in the case of N-alkylated and N,N′-dialkylated salts forhalides, trifluoromethanesulfonate or other anions which increase thesolubility.

It is possible to use as optical indicator or as optical indicatorsystem any substance which is reducible and on reduction experiences adetectable change in its optical properties such as, for example, color,fluorescence, reflectance, transmission, polarization or/and refractiveindex. Determination of the presence or/and the amount of the analyte inthe sample can take place with the unaided eye or/and by means of adetection device using a photometric method which appears to be suitableto a person skilled in the art. Heteropolyacids and in particular2,18-phosphomolybdic acid are preferably used as optical indicators andare reduced to the corresponding heteropoly blue.

The alteration in the coenzyme is particularly preferably detected bymeasuring the fluorescence. Fluorescence measurement is highly sensitiveand makes it possible to detect even low concentrations of the analytein miniaturized systems.

An alternative possibility is also to detect the alteration in thecoenzyme electrochemically using a suitable test element such as, forexample, an electrochemical test strip. The precondition for this isonce again the use of suitable mediators which can be converted by thereduced coenzyme, by transfer of electrons, into a reduced form. Theanalyte is determined by measuring the current which is needed toreoxidize the reduced mediator and which correlates with theconcentration of the analyte in the sample. Examples of mediators whichcan be used for electrochemical measurements include in particular theaforementioned mediators employed for photometric measurements.

It is possible to use a liquid test to detect an analyte, in which casethe reagent is for example in the form of a solution or suspension in anaqueous or nonaqueous liquid or as powder or lyophilizate. However, itis also possible to use a dry test, in which case the reagent is appliedto a support, a test strip. The support may include for example a teststrip including an absorbent or/and swellable material which is wettedby the sample liquid to be investigated.

A particularly preferred test format includes the use of the enzymeglucose dehydrogenase with a stable NAD derivative for detectingglucose, in which case a derivative of the reduced coenzyme NADH isformed. NADH is detected by optical methods, e.g. by photometric orfluorometric determination after UV excitation. A particularly preferredtest system is described in US 2005/0214891, to which express referenceis made here.

In particular, the stable test chemical can be configured to comprise anenzyme stabilized with a stable coenzyme, where the stabilized enzymeshows on storage for preferably at least two weeks, particularlypreferably at least four weeks and most preferably at least eight weeksat a temperature of, preferably, at least 20° C., particularlypreferably at least 25° C. and most preferably at least 30° C., whereappropriate with high air humidity and without a drying reagent, adecline in the enzymatic activity of less than 50%, preferably less than30% and most preferably less than 20% compared with the initial level.

Other types of stable test chemicals can also be used alternatively oradditionally, for example the test chemical described in WO 2007/012494A1 (see also, US 2008/213809). In principle, the test chemical can becontained in a test element in any desired manner. The test chemicaland/or the test element may be suitable for carrying out dry or liquidtests. By way of example, the test chemical can be applied on a suitablecarrier material for this purpose, for example on a plastic and/or aceramic material and/or a paper material.

When a test chemical which is at least substantially stable with respectto ambient influences is used, as in the manner provided by the secondaspect of the present invention, it is possible to have recourse tobetter and more precise connection techniques for producing the housingand/or to a larger choice of materials. Accordingly, the second aspectof the present invention proposes configuring the analytical magazine insuch a way that the latter has a housing with at least two components,for example two magazine halves. In this case, the two parts need notnecessarily be configured identically. The housing, in particular the atleast two parts together, can form the at least two chambers. It isparticularly preferred for the at least two parts to be connected to oneanother by a method without using an adhesive. In particular, cohesiveconnection methods without an adhesive are appropriate here. The use ofat least one laser welding method is particularly preferred on accountof the high precision and the low degree of contamination caused.Accordingly, the second aspect of the invention proposes connecting theat least two components to one another by means of a laser weldingmethod.

With a laser welding method it is possible to obtain uniform weldingseams with a small width and high precision, where the method at thesame time is thermally well controllable and localizable and can also becarried out practically without any contamination.

Particularly when a laser welding method is used, it is appropriate, asis likewise proposed according to the invention, if a first of the atleast two components and a second of the at least two components have adifferent transparency. By way of example, a first of the at least twoparts can be configured such that it is almost completely transparent,and a second of the at least two parts can be configured such that it isabsorbent within the wavelength range used for the laser welding method.In this case, the at least two components can preferably comprise thesame basic material, but in each case with a different absorption forlight in the visible and/or infrared and/or ultraviolet spectral range.By way of example, the at least two parts can have a differentabsorption in a spectral range of between 500 and 1200 nm, in particularin a spectral range of 700 to 1100 nm or 700 to 1000 nm, in whichconventional lasers used for the laser welding emit, for examplesemiconductor lasers and/or Nd:YAG lasers. In order to achieve adifferent transparency or absorption of the at least two components, abasic material of the components, which can also be identical for bothcomponents, can be colored differently, for example by the basicmaterial (for example polycarbonate, PC) of one of the parts beingadmixed with a dye in order to reduce a transparency. By way of example,the two components could have, in said wavelength range, a difference intransparency of at least 5%, preferably of at least 20% and particularlypreferably of at least 50% for the laser radiation used. In this case, atransparency is understood to mean a transmittance.

If a welding method is used for connecting the at least two parts, thenthe welding seams can have for example a width of at most 0.5 mm, inparticular of at most 0.3 mm and particularly preferably of at most 0.2mm. As will be explained below, this makes a considerable contributionto increasing the packing density. In particular, it once againadvantageously becomes apparent here that the test chemical is at leastsubstantially stable with respect to ambient influences since a transferof moisture from one chamber into another chamber is largely irrelevantin this case.

Generally, a multiplicity of materials can be used for the housing, inparticular for the at least two components of the housing, for examplefor the two magazine halves. In particular, thermoplastics can be used.One particular advantage of the use of a test chemical which is at leastsubstantially stable with respect to ambient influences consistsprecisely in the fact that these plastics do not have to satisfy specialrequirements with regard to imperviousness to moisture. Accordingly, thechoice and design of the plastics can be effected for example accordingto other criteria, for example according to processability in a specificshaping process, for example during injection molding. It is alsopossible to have recourse to cost-effective materials. By way ofexample, one or more of the following plastics can be used: PC(polycarbonate); ABS (acrylonitrile-butadiene-styrene); COC (cycloolefincopolymers); PMMA (polymethyl methacrylate); PS (polystyrene); PET(polyethylene terephthalate). These materials have advantages withregard to their processing properties and/or with regard to their costs,but can be used only poorly, in principle, if the requirement for vaportightness also has to be met.

PC has for example a high resistance to ionizing radiation and a hightransparency for a broad spectrum. It is a cost-effective mass-producedmaterial which, however, has a comparatively high permeability to watervapor. However, since this permeability is largely irrelevant, inprinciple, in the context of the present invention, particularly whenthe stable test chemical is used, and since the processing properties ofthis material are particularly good in practice, this material isparticularly preferred in the context of the present invention.

ABS can be processed very well and, in particular, can beinjection-molded very well, such that the use of this material is alsoadvantageous. This material, too, has a comparatively good transparencyfor a broad light spectrum and also low costs.

COC admittedly has a high transparency in a broad spectral range fromultraviolet light through to the infrared spectral range and provides agood vapor barrier, but is comparatively expensive and only moderatelystable with respect to ionizing radiation.

PMMA has only little or no intrinsic fluorescence at all in theultraviolet spectral range and also has a good transparency for a broadlight spectrum. The high vapor permeability of this material istolerable in the context of the present invention, particularly when thestable test chemical is used, and it is a cost-effective material.Therefore, this material, too, can be used advantageously in the contextof the present invention.

PS can be processed well, in particular by an injection-molding method.It has a good transparency for a broad light spectrum. Moreover, it is acost-effective mass-produced plastic. Overall, therefore, this material,too, can be used successfully in the context of the present invention.

With this extended choice of materials that is no longer restricted bythe requirement for vapor impermeability, it is possible, in principle,for the preferably at least two parts of the housing of the analyticalmagazine to be connected by means of laser welding, instead of aconventional one of ultrasonic welding and/or an adhesive-bondingmethod, which would be left for non-transparent materials. Identicalmaterials can be welded in a very simple manner for example by means ofa laser, for example PC to PC and/or COC to COC, etc., particularly ifone part is light-absorbent for the laser wavelength, for example bymeans of corresponding coloration and/or doping, and the other part isconfigured such that it is transparent or more transparent. Althoughopaque parts can, in principle, also be irradiated in such a way thatwelding is possible, the welding seams then generally become coarser andneed more space. By contrast when the parts to be connected to oneanother have high transparency and smooth surfaces, it is possible toobtain very narrow welding seams, for example welding seams having theabovementioned width of 0.3 mm. These small welding seams allow theanalytical magazine to be made very small, for example with thepreferred packing densities described above. Furthermore, in the case oflaser welding it is possible to avoid the formation of dust, whichusually occurs in other welding methods, for example in ultrasonicwelding. Such formation of dust can become apparent in a negative wayparticularly in the case of analytical aids or sub-aids in the form oftest elements since a test chemical of the test elements can becontaminated by dust and other contaminants which can occur duringwelding. If, as an alternative or in addition, lancets and/ormicrosamplers are used as analytical aids or as analytical sub-aids,then that likewise makes formation of dust apparent in a very negativeway since, by way of example, hydrophilicity of the lancets and/ormicrosamplers can be influenced by the dust. This can be avoided by theuse of the laser welding method. Furthermore, vibrations that mightresult in resonance of structures or parts of the analytical magazine donot occur. Moreover, no additional materials are required either, suchas adhesives, for example, which might contaminate the interior of thechambers and/or the analytical aids, thereby jeopardizing hydrophilicityof lancets or microsamplers, for example.

Moreover, in particular by using laser welding and/or the preferredplastics, new methods become possible for closing off and/or sealing theanalytical magazine, for example for sealing a finished analyticalmagazine. Hitherto, in many cases analytical magazines have been closedoff thermally using films capable of being bonded by hot melt adhesives.However, the hot melt adhesives used in this case can influence theanalytical aids, under certain circumstances. Thus, by way of example,vapors of the hot melt adhesive can influence lancets and/ormicrosamplers, for example can impair the hydrophilicity thereof. Bymeans of the proposed invention, in particular using the laser weldingmethod and/or the materials proposed, however, it is possible to use, asan alternative or in addition to, for example, metal films, e.g.aluminum films, for sealing the analytical magazine, one or more plasticfilms which, by way of example, can be welded by means of a laserinstead of being adhesively bonded.

Overall, the newly acquired freedom with regard to the choice ofmaterials thus affords a basis for a considerably more compact system.This is not only because the analytical magazine can be configured witha considerably smaller structural space and/or a considerably higherpacking density. The analytical magazine can also be simplified greatlyin terms of its production and/or its handling and be made morecost-effective.

The analytical magazine has in general, in particular in the secondaspect of the present invention, preferably one or more of the followingproperties: a total volume of not more than 10 cm³; an external radiusof not more than 5 cm; an internal radius of between 0.5 cm and 2 cm; athickness of not more than 1 cm; a number of analytical aids of 10 to100; a volume of between 3 cm³ and 30 cm³; a packing density of theanalytical aids of more than 5/cm³.

It is particularly preferred if an external volume of the analyticalmagazine, that is to say a volume without taking account of holes orother openings in the analytical magazine, does not exceed 5 cm³,preferably 3 cm³ and particularly preferably 2 cm³. By way of example,the external volume can be 1.94 cm³. It is particularly preferred if anempty volume of the analytical magazine, that is to say a total volumeof openings optionally present in the analytical magazine, does notexceed 0.8 cm³, preferably 0.5 cm³ and particularly preferably 0.4 cm³.By way of example, the empty volume can be 0.39 cm³. The openings can befor example inner openings of a disk-shaped analytical magazine intowhich, by way of example, a drive can engage. Said empty volume is notintended to encompass the interior space inside the housing, for examplethe chambers. In this case, a net volume is understood, in the contextof the present invention, generally to mean the external volume minusthe empty volume. Consequently, in the case of a circular-disk-shapedmagazine, a volume results which essentially results from the diameterand the height of the circular disk, and, in the case of anannular-disk-shaped magazine, a net volume results which results inrelation to the net volume of a corresponding circular disk bysubtracting the volume of a central cutout. Accordingly, it is preferredif the net volume of the analytical magazine, that is to say theexternal volume minus the empty volume, does not exceed 5 cm³particularly preferably 3 cm³, and in particular does not exceed 2 cm³.By way of example, the net volume can be 1.55 cm³.

In the context of the present invention, a packing density is generallyunderstood to mean a number of analytical aids per net volume of theanalytical magazine. As explained above, however, each analytical aidcan comprise a plurality of sub-aids which can interact with oneanother, for example in each case as a test. Preferably, each analyticalaid comprises as sub-aid a test element with at least one test chemical.In addition, each analytical aid can then comprise as further sub-aid atleast one lancet which serves for the sample generation of a sample ofbody fluid, which is then applied to the associated test element. If ananalytical aid contains a plurality of analytical sub-aids, thenassociated analytical sub-aids still count as an analytical aid,however, for the calculation of the packing density, for example by atest element and an associated lancet being counted as a commonanalytical aid. By way of example, in each case exactly one analyticalaid with at least one test element and optionally at least one lancetcan be received in a respective chamber. As explained above, however,other configurations are also possible.

Thus, the analytical magazine can be configured as an annular disk, forexample, having an external diameter of less than 100 mm, for example 50mm, and an internal diameter of a cutout of the annular disk of lessthan 50 mm, for example 22.5 mm. The analytical magazine can have forexample a thickness of less than 5.0 mm, for example a thickness of 3.1mm. The analytical magazine can preferably comprise more than 20analytical aids, for example at least 50 analytical aids and even 100analytical aids or more. By way of example, 50 analytical aids eachhaving a test element and optionally each additionally having a lancetcan be provided, where in each case a test element and an associatedlancet count as an analytical aid, also called “test”. By way ofexample, in each case one analytical aid of this type can be received ina respective chamber. Accordingly, the packing density can be forexample at least 50 analytical aids/5 cm³=1 analytical aid/0.1 cm³,preferably at least 50 analytical aids/3 cm³=1 analytical aid/0.06 cm³and particularly preferably at least 50 analytical aids/2 cm³=1analytical aid/0.04 cm³. By way of example, the packing density can be50 analytical aids/1.55 cm³=1 analytical aid/0.031 cm³. A differentconfiguration of the analytical magazine as a configuration as acircular disk is also possible, however, for example with one or more ofthe geometries described above. A configuration as a tape magazine isalso possible, for example, in which case, for example, one chamber ofthe tape magazine comprises a good winding with analytical aids thathave not yet been used, and another chamber of the tape magazinecomprises a poor winding, on which analytical aids that have alreadybeen used can be received.

High packing densities can also be achieved, in particular, by virtue ofthe fact that the analytical aids are mounted very close together,without a hermetic separation between the analytical aids having to beeffected. In this regard, the use of the stable test chemical becomesapparent in a particularly advantageous way. Thus, by way of example, itis possible to use analytical magazines which have a housing having awall thickness of at most 1.2 mm. In this case, a wall thickness shouldbe understood to mean a thickness of the housing between a chambercomprising an analytical aid and the surroundings or an adjacentchamber, in particular at a thinnest location of the housing. It isparticularly preferred if the wall thickness is not more than 1.0 mm,and in particular not more than 0.8 mm. By way of example, the wallthickness of from 0.3 mm to 0.8 mm can be chosen.

Once again as an alternative or in addition, the use of a drying agentsuch as activated carbon, for example, can be dispensed with in theanalytical magazine. Accordingly, it is particularly preferred if theanalytical magazine is configured in a manner free of drying agent. Inthis way, too, structural space can be saved.

If such a stable test chemical is used, then a moisture-impermeableconfiguration of the separation of the individual chambers can also becompletely dispensed with, in principle. The analytical magazine cantherefore generally comprise a plurality of analytical aids which arereceived in at least two chambers. In this case, the analytical aids canin turn each comprise at least one test element with at least one testchemical for detecting at least one analyte in a liquid sample, inparticular a body fluid, wherein the test chemical is configured in sucha way that it is at least substantially stable with respect to ambientinfluences, in particular with respect to moisture. In this case, ingeneral in the second aspect of the invention, but also in the firstaspect described above, the chambers can be configured such that theyare separated from one another in such a way that moisture can beexchanged between the chambers, for example between adjacent chambers.By way of example, the chambers can have chamber walls, wherein gaps orother openings are provided in or alongside the chamber walls,preferably with an opening width of not more than 20 μm, in particularof not more than 10 μm. These opening widths on the one hand enable airhumidity to be exchanged between the chambers, but generally hold backcoarser contaminants or germs.

The analytical magazine in one or more of the configurations describedabove can additionally be advantageously refined in various ways. Inparticular, as explained above, an analytical aid can comprise in eachcase a test element with a test chemical, in particular the testchemical which is stable with respect to ambient influences, and alancet. These sub-aids can be stored jointly in one and the samechamber, for example in each case a pair comprising a lancet and a testelement in one chamber, or a plurality of such pairs in a commonchamber. The use of the test chemical which is stable with respect toambient influences, in particular air humidity and/or beta radiation,enables a primary requirement for separate packaging of lancets and testelements to be obviated. Furthermore, the need to package the testchemical tightly against water vapor and/or to insert a drying agentinto the chambers and/or the analytical magazine can also be obviated.As a result, new concepts become possible in particular for a combinedanalytical magazine with lancets and test elements. It is not necessaryfor the lancets and the test elements to be stored separately from oneanother. In addition, as will be explained in even greater detail below,other materials are possible for the magazine parts since it is nolonger necessary simultaneously to satisfy the requirements forradiation stability and vapor tightness together.

Since a barrier between the analytical aids, in particular betweenlancets and test elements, can be dispensed with, a considerably morecompact arrangement of lancet elements and test elements can beeffected, for example in the same chamber of the analytical magazine.The lancet tip can lie closely alongside the test chemical in the caseof storage in the chamber, for example, which, after a sample has beenobtained, is also suitable as a position for transferring the sample tothe test chemical. As a result, a mechanism for actuating the analyticalaid can be designed considerably more simply than in the case ofconventional analytical magazines since, by way of example, anadditional movement for the purpose of overcoming a second barrier, as abarrier between lancet and test element, can be dispensed with and sinceit is not necessary to move to an additional position with the lancet.In contrast to previous concepts with separate packaging of lancet andtest chemical, the test chemical also need not necessarily be moved inorder to remove it from its packaging. In this case, generally it isonly necessary for the lancet to be docked to a corresponding actuatorand moved.

Accordingly, a further method for producing an analytical magazine isfurthermore proposed in an additional aspect of the present invention.The analytical magazine can be, in particular, an analytical magazine inaccordance with one or more of the configurations described above and/oran analytical magazine which can be produced in accordance with a methodin accordance with one or more of the configurations described above.However, other configurations are also possible, in principle.

The analytical magazine is designed to receive a plurality of analyticalaids in a plurality of chambers. The analytical aids each have at leastone test chemical. In particular, this can be a test chemical which isat least substantially stable with respect to ambient influences inaccordance with the above description. The test chemical can be forexample part of test elements which are received preferably completelyin the housing, for example in the chambers. In the method according tothe invention, a plurality of analytical aids are introduced into atleast one of the chambers. By way of example, exactly one analytical aidcan be introduced per chamber, or a plurality of analytical aids can beintroduced into one chamber. The analytical magazine furthermore has ahousing with at least two components. The at least two components areconnected to one another by a laser welding method before or after theprocess of introducing the analytical aids into the at least onechamber. The analytical aids can additionally have in each case at leastone lancet. These lancets preferably have at least one capillary channelfor taking up body fluid, which is passed to the test element via thelancet. Advantageously, such a capillary channel of the lancet (forexample of a needle element), in particular a capillary structure, iscoated, preferably hydrophilically coated, in order to enable improvedtransport of the body fluid. The analytical magazine can furthermore besterilized using ionizing radiation, in particular after the laserwelding method has been carried out. For the advantages of the proposedmethod in one or more of the configurations described, reference maylargely be made to the description above. In particular, the laserwelding method has the effect that a high packing density can berealized and that the analytical aids, in particular the lancets, duringthe production method, are not contaminated or are contaminated only toan insignificant extent, for example with dust that might deposit on thehydrophilic coating of the lancet.

DRAWINGS

Further details and features of the invention will become apparent fromthe following description of preferred exemplary embodiments. In thiscase, the respective features can be realized by themselves or as aplurality in combination with one another. The invention is notrestricted to the exemplary embodiments. The exemplary embodiments areillustrated schematically in the figures. In this case, identicalreference numerals in the individual figures designate identical orfunctionally identical elements, or elements which correspond to oneanother with regard to their function.

FIGS. 1A and 1B show different perspective illustrations of a firstcomponent of an analytical magazine;

FIGS. 2A and 2B show provision of a plurality of analytical aids in theform of lancets;

FIG. 3 shows the first component in accordance with FIGS. 1A and 1Bafter insertion of the lancets in accordance with FIGS. 2A and 2B;

FIG. 4 shows a perspective illustration of a second component of theanalytical magazine;

FIG. 5 shows a perspective illustration of the analytical magazine afterapplication of the second component in accordance with FIG. 4;

FIG. 6 shows an exemplary illustration of a sealing element for sealingopenings of the analytical magazine; and

FIGS. 7A and 7B show different perspective illustrations of a finishedanalytical magazine.

DETAILED DESCRIPTION

The following description of technology is merely exemplary in nature ofthe subject matter, manufacture and use of one or more inventions, andis not intended to limit the scope, application, or uses of any specificinvention claimed in this application or in such other applications asmay be filed claiming priority to this application, or patents issuingtherefrom.

One possible embodiment of a method according to the invention forproducing an analytical magazine 110 and also an exemplary embodiment ofsuch an analytical magazine 110 are described below with reference toFIGS. 1A-7B. The finished analytical magazine 110 is illustrated inFIGS. 7A and 7B. In this case, the analytical magazine 110 constitutesan exemplary embodiment of the above-described first aspect of theinvention, in which a plurality of analytical aids are introduced into ahousing simultaneously during production. However, the analyticalmagazine can also function as an exemplary embodiment of theabove-described second aspect of the invention, according to which alaser welding method is used as the connection technique.

In a first method step, which is illustrated in FIGS. 1A and 1B, a firstcomponent 112 of the analytical magazine 110 is provided. In this case,FIG. 1A shows a view of the first component 112 from below, that is tosay a perspective illustration obliquely from a side of the firstcomponent 112 which faces away from the interior of the analyticalmagazine 110, whereas FIG. 1B shows a perspective illustration obliquelyfrom above, that is to say from a side which faces the interior of theanalytical magazine 110 in the assembled state of the analyticalmagazine 110.

As can be discerned from the illustrations, the first component 112, aswell as the analytical magazine 110 as a whole, is configured in theform of an annular disk, with an outer circumferential side 114 and acircular inner opening 116. An analytical system which uses theanalytical magazine 110, said system not being illustrated in thefigures, can, by way of example, receive the analytical magazine 110completely or in part and can engage into the inner opening 116completely or in part. Thus, by way of example, an actuator and/or acentering of the analytical system can engage into the toothing of theinner opening 116 completely or in part. The analytical system can have,by way of example, a corresponding transport device which interacts withtransport elements 118 (see, for example, FIG. 5 below) on theanalytical magazine 110, for example in order to bring about furthertransport, for example cyclic advance, of the analytical magazine 110.In this regard, reference may be made to the prior art, for example. Thetransport elements can comprise for example corresponding grooves,teeth, hooks, pins, projections, depressions or the like. The transportelements 118 are illustrated for example in FIG. 5, which is describedin greater detail below, where they are configured in pin form by way ofexample. Furthermore, the analytical magazine 110 optionally comprisesnotches 119 in FIG. 1A. These notches 119 may serve for example forpositioning in an assembly device, such as the outer one of the notches119 in the example illustrated. In the example illustrated, the innernotch 119 serves for lowering a gate during production by means of ashaping method, for example an injection-molding method.

As illustrated in FIGS. 1A and 1B, the first component 112 can thus beconfigured for example as an annular disk and can be produced forexample completely or partly from a plastic material. The firstcomponent 112 has a plurality of receptacles 120, which form parts ofchambers 122 in the assembled state of the analytical magazine 110.These receptacles 120 and chambers 122 can be discerned in FIG. 1B. Ascan be seen from this illustration, the receptacles 120 in the exemplaryembodiment illustrated are arranged radially and have correspondingdepressions in the first component 112. The receptacles 120 arepreferably just wide enough that a puncturing and collecting element,described in greater detail below, as an analytical aid and/or sub-aid,can just be mounted in said receptacles 120. Accordingly, by way ofexample, the outer dimensions of the receptacle 120 can correspond tosaid analytical aids, plus an amount of play, if appropriate, forexample in each case a few hundreds of a millimeter in one or moredimensions, in the form of a gap, for example, which can ensure themobility of the puncturing and collecting elements or analytical aids.

On the opposite side, that is to say on the side facing away from thereceptacles 120, the first component 112 has an annular groove 124 inthe exemplary embodiment illustrated. Openings 126 are respectivelyprovided within said annular groove 124 in the exemplary embodimentillustrated, in each case one of said openings 126 being provided perchamber 122 in the exemplary embodiment illustrated. Said openings 126are embodied in the form of elongate, radially extending slots in theexemplary embodiment illustrated. In the exemplary embodimentillustrated, said openings 126 subsequently serve as test elementopenings 128 or test field windows which respectively define a testfield accessible from the chambers 122. This is explained in greaterdetail below.

Alongside the test element openings 128, the chambers 122 have furtheropenings 126 in the exemplary embodiment illustrated. These openings 126have in part already been formed in the first component 112, but canalso be included wholly or in part in further components of theanalytical magazine 110. Thus, the receptacles 120 in the exemplaryembodiment illustrated, as can be seen from FIG. 1B, in particular, haveopenings 126 on the outer circumferential side 114, which openingssubsequently serve as sampling openings 130. Through these samplingopenings 130, the analytical aids can emerge completely or in part for asampling movement. Furthermore, the receptacles 120 have openings 126 onthe side facing the inner opening 116, which openings function asactuator openings 132 during subsequent operation of the analyticalmagazine 110 and enable an actuator (not illustrated) to enter insidethe chambers 122, for example in a chamber 122 of the analyticalmagazine 110 which is currently situated in an application position.

In a further method step, illustrated in FIGS. 2A and 2B, a plurality ofanalytical aids 134 are provided. In the case illustrated, these arelancets 136 in the form of microsamplers which can form in each case ananalytical aid 134 or a sub-aid of these analytical aids 134. In thiscase, FIG. 2A shows a perspective overall illustration of the lancets136 provided, whereas FIG. 2B shows a detail illustration. In theexemplary embodiment illustrated, the lancets 136 are configured asmicrosamplers and have a tapered lancet end 138 facing outward with alancet tip, and also a widened lancet body 140 in each case. At theopposite end with respect to the lancet tip, the lancets 136 cancomprise one or more coupling elements 141 for coupling an actuator, forexample an eye, a pilot hole or the like. Each lancet 136 has acapillary channel 137, for example a capillary gap, which is indicatedby a dashed line in FIG. 2B and which serves for taking up a bloodsample. The lancets 136 can be worked, for example etched, as flatlancets, from a metal disk 142, which can be discerned in FIG. 2A. Themetal disk 142 can carry for example a single radial lancet arrangementor a plurality of lancet arrangements which, by way of example, can beapplied successively into different magazine housings.

The metal disk 142 and/or parts of said metal disk 142 serve as aholding element 144, by means of which the lancets 136 areinterconnected. Said holding element 144 can comprise an etching grid,for example, which was etched from the metal disk 142. The lancets 136can be connected to the holding element 144 by connecting elements 146,which can be part of the holding element 144 or which can also directlyform the holding element 144, for example by means of the lancets 136being interconnected directly by means of webs or the like. Theconnecting elements 146 can act for example in tapered portions147—which can be discerned in FIG. 2B—in the lancet body 140. Theconnecting elements can comprise desired braking locations, inparticular, which enable the lancets 136 to be broken more easily fromthe assemblage illustrated in FIGS. 2A and 2B. The tapered portions 147ensure that braking burrs are offset inward from the edge of the lancetbody 140, such that these braking residues do not impede movement of thelancets 136 in the chambers 122.

The lancets 136 are provided in radial orientation by means of theholding element 144 in the case of the provision in FIGS. 2A and 2B,such that a lancet 136 is respectively oriented in a mannercorresponding to the receptacles 120 in FIG. 1B. Afterward, theanalytical aids 134 or lancets 136 connected to one another in this wayare optionally separated from the holding element 144, for example bybeing broken out, and laid into the receptacles 120 of the firstcomponent 112 and separated from the holding element 144, for example bybeing broken out. The process of breaking out can be effected beforeand/or after the process of laying into the receptacles 120. The resultof these method steps is illustrated in FIG. 3. The illustration here isanalogous to FIG. 1B, and so reference may largely be made to saidfigure.

The process of laying the analytical aids 134 or lancets 136 into thereceptacles 120 can be effected for example by the holding element 144being gripped by means of a suction unit, a gripper or similar devicesand being correspondingly positioned. This process can be effectedautomatically or else manually. The metal disk 142 and/or the holdingelement 144 can comprise further positioning aids for this purpose, forexample the positioning openings 145 indicated in FIG. 2A. Theanalytical aids 134 or the connecting elements 146 can be separated forexample by mechanical stamping, exertion of pressure or similarseparating methods, for example the braking described above. In thiscase, the individual lancets 136 can be fixed for example on aseparating tool, for example magnetically and/or by means of a vacuumfixing or a similar fixing device, in particular until the lancets 136lie in their respective chambers 122.

This illustration reveals that one purpose of the receptacles 120 mayconsist in fixing the analytical aids 134 at least in part in terms oftheir spatial orientation after separation from the holding element 144.The receptacles 120 can be configured accordingly, in which case theyneed not necessarily comprise depressions, as illustrated in thefigures, and so said depressions can for example also be replaced byother elements and/or be configured with a depth as small as desired, inprinciple. However, the embodiment illustrated is preferred on accountof the good fixing, the depth of the receptacles 120 preferably beingmade at least equal to the depth of the lancets 136 or of the analyticalaids 134.

The process of separating the analytical aids 134 can be effectedbefore, during or after the process of inserting the analytical aids 134into the receptacles 120. Thus, by way of example, a process ofseparating can be effected after the process of laying in and/or alreadywhile the analytical aids 134, still connected to one another by meansof the holding element 134, are positioned in a manner hanging above thefirst component 112. The process of separating can be effectedsimultaneously in particular for all of the analytical aids 134 or for aplurality of analytical aids 134, such that, by way of example, all ofthe lancets 136 can be broken from the holding element 144 or theetching grid all at once, whereupon they can fall into the underlyingreceptacles 120.

In a further method step, it is possible to close off the receptacles120 with the analytical aids 134 received therein. This can be effected,in principle, by applying any desired second component 148, which, byway of example, can also be configured in the form of a film. In anoptional case illustrated in FIG. 4, however, the second component 148is configured for example as an annular disk which functions as an upperpart. This annular disk, where FIG. 4 shows a view obliquely from below(that is to say a view from the chambers 122) of said second component148, can for example likewise be produced from plastic and is preferablyconfigured such that it is substantially rigid.

The second component 148 can comprise a plurality of elementscorresponding to the receptacles 120. In the exemplary embodimentillustrated, the second component 148 comprises a plurality ofdepressions 150 which correspond to the receptacles 120 and which arelikewise configured in radial fashion. By way of example, as indicatedin FIG. 4, said depressions 150 can in turn comprise openings 126 on theouter circumferential side 114 and/or on the side facing the inneropening 116. Said openings 126 can subsequently form part of thesampling openings 130 and/or actuator openings 132.

Furthermore, the second component 148 comprises a plurality of ribs 152which are likewise arranged in a manner corresponding to the receptacles120. Said ribs can impose elastic bending on the analytical aids 134,for example the lancets 136 or samplers, if appropriate together withcurved bottoms of the receptacles 120 of the first component 112, and inthis way secure them against falling out.

FIG. 5 illustrates the analytical magazine 110 or a semifinished part ofsaid analytical magazine 110 after the second component 148 has beenapplied to the first component 112 shown in FIG. 3. A perspectiveillustration obliquely from above is shown here, with the view directedat the second component 148. The second component 148 and the firstcomponent 112 can be connected to one another, for example, inparticular by means of a welding method, for example laser welding. Forthis purpose, by way of example, one of the components 112, 148 can beconfigured such that it is transparent to laser radiation, whereas therespective other of said components 112, 148 can be configured such thatit is absorbent for the laser radiation. In particular, the twocomponents 112, 148 can therefore be produced from materials havingdifferent absorption properties. The use of one or more of the plasticspresented above is particularly preferred. In this case, for the twocomponents 112, 148 it is possible to use identical basic materials, inprinciple, for example identical plastics, which differ in theirabsorption properties, however, for example through a mixture ofadditives such as dyes, for examples. In this way, in particular in awavelength range of between 500 nm and 1200 nm, in particular between700 nm and 1100 nm, it is possible to create a difference in anabsorption of the components 112, 148 and/or of constituent parts ofsaid components 112, 148, for example a difference in an absorption ofat least 20%, preferably at least 50% or even at least 80% or more.

It can be discerned from the figures that the second component 148 canprovide transport elements 118, for example, on its top side, whichcannot be discerned in FIG. 4. Furthermore, this being discernible onlywith difficulty in FIG. 4, it is clearly discernible in FIG. 5 that thesecond component 148 provides a plurality of further openings 126 in theform of transfer openings 154. These transfer openings 154 can beconfigured for example in such a way that in each case one of saidtransfer openings 154 is provided per chamber 122. Accordingly, thetransfer openings 154, which are illustrated as round transfer openings154 in the exemplary embodiment illustrated, are arranged in circularfashion on the top side of a housing 156 of the test element magazine110, said housing being formed by the first component 112 and the secondcomponent 148. However, other configurations are also possible, inprinciple.

The transfer openings 154 in the second component 148 subsequentlyserve, during the use of the analytical magazine 110, for example in ananalytical system, to enable a sample to be transferred from a lancet136 to a test field 170, which is described in greater detail below.Accordingly, for example an actuator, for example a plunger, canpenetrate through a transfer opening 154 into a chamber 122, for examplea chamber 122 situated in an application position of an analyticalsystem, and press the sample-laden lancet 136 (or the microsampler) ontothe test field 170, such that the sample is transferred from the lancet136 to the test field 170. The transfer openings 154 can therefore alsoserve as actuator openings 132 and are correspondingly designated assuch in the figures.

In a further method step, a test chemical 158 is then applied on theunderside of the housing 156. This is indicated in FIG. 7B. Said testchemical 158 can be configured for example in the form of a testchemical field 160, in particular a continuous test chemical field 160,preferably in the form of a ring-shaped test chemical field 160. Thetest chemical 158 is preferably configured in such a way that it is atleast substantially stable with respect to ambient influences, inparticular with respect to air humidity. Stability with respect toconventional ionizing radiations used for sterilization is alsoadvantageous. For possible configurations of the test chemical 158,reference may be made to the description above.

The test chemical 158 can be applied for example to a carrier 164, forexample a likewise annular carrier 164, which is preferably configuredas a continuous carrier 164 for all of the chambers 122, preferably asan integral carrier 164. The carrier 164 and the test chemical field 160together form a continuous chemical ring 162 in this exemplaryembodiment. By way of example, the carrier 164 can be configured in theform of a self-adhesive or non-adhesive film and/or a plastic carrier.Other carrier materials are also possible, in principle. Said carrier164 with the test chemical 158, which is arranged on the top side of thecarrier 164 in the illustration shown in FIG. 7B, is introduced into theannular groove 124 on the rear side of the first component 112 in theexemplary embodiment illustrated. The test element openings 128 arepreferably completely closed off by the test chemical 158 and thecarrier 164, such that the carrier 164 and/or the test chemical 158 cansimultaneously also act as a seal 166 of the test element openings 128.As an alternative or in addition, however, an additional seal 166 canalso be provided. The latter can be applied for example on the rear sideof the carrier 164 after the application of the carrier 164 into theannular groove 124, for example by means of an adhesive-bonding methodand/or laminating method.

The carrier 164 and/or the test chemical field 160 are preferablycompletely covered with the test chemical 158. In the regions in whichthe test chemical field 160 covers the test element openings 128, theregions 168 of the test chemical field 160 respectively form test fields170 which face the interior of the chambers 122 and which thereforelikewise form part of the analytical aids 134, or sub-aids.

The test chemical 158 then lies directly below the lancets 136 in thechambers 122, and each of the chambers 122 is separated from the nextchamber 122. Only the sampling openings 130, the actuator openings 132and the transfer openings 154 are still open. If a sampling movement isthen carried out by means of the lancet 136, body fluid, in particularblood, can be taken up by the capillary channel 137, for example bymeans of a capillary effect, and/or a surface effect of the lancet 136.As a result of the lancet 136 moving back into the chamber 122, the bodyfluid then passes into the vicinity of the test chemical 158, such thatthe sample can be transferred from the lancet 136 to the test chemical158 or the corresponding test field 170 of the chamber 122 currentlybeing used.

In order that the chambers 122 that are not currently being used areprotected against ambient influences, in particular moisture, thefurther openings 126 can be sealed in a method step which precedes,takes place in part at the same time as, or succeeds, the method step inFIG. 7. Thus, FIG. 6 illustrates by way of example a seal 166 which canbe used in order, by way of example, to seal the measurement openings154 and/or the actuator openings 132 and/or the sampling openings 130simultaneously or successively. Said seal can comprise for example around sheet composed of thin aluminum film or similar film-typeelements. The seal 166, which can also be formed in multipartitefashion, can be preformed by means of a deep-drawing method, forexample. The seal 166 can be connected to the housing 156 for example ina positively locking manner and/or cohesively and/or in a force-lockingmanner, for example by adhesive bonding and/or lamination.

In FIG. 7A, the analytical magazine 110 is finally illustrated in sealedform. As explained above, said analytical magazine can be laid forexample into an analytical system in which the analytical magazine 110can be rotated about an axis of rotation by means of a correspondingtransport mechanism, for example, in order to move for example arespective one of the chambers 122 into at least one applicationposition, for example for a sampling movement. Furthermore, furtherpositions can be provided, for example measurement positions, in which ameasurement of color changes and/or changes in other properties of thetest fields 170 can be measured through the measurement openings 154,for example.

In the application position, on the inner circumference facing the inneropening 116, an actuator, for example an actuator comprising at leastone actuating plunger, can engage, for example puncture, into thechamber 122 respectively situated in the application position, in whichcase (for example simultaneously and/or beforehand) the seal 166 of theactuator opening 132 of the chamber 122 situated in the applicationposition can be opened, for example pierced. Through the seal 166, forexample the film, on the outer circumferential side 114, the samplers inthe form of the lancets 136 then emerge upon actuation.

A measurement of changes in the properties of the test fields 170 can beeffected for example from an outer side of the analytical magazine 110,for example through the carrier 164 of the test chemical 158. For thispurpose, the carrier 164 can be configured for example such that it iswholly or partly transparent, such that, by way of example, in FIG. 7B,a measurement of color changes can be effected from the underside of thetest element magazine 110.

LIST OF REFERENCE SYMBOLS

-   110 Analytical magazine-   112 First component-   114 Outer circumferential side-   116 Inner opening-   118 Transport element-   119 Notches-   120 Receptacles-   122 Chambers-   124 Annular groove-   126 Openings-   128 Test element openings-   130 Sampling openings-   132 Actuator openings-   134 Analytical aids-   136 Lancets-   137 Capillary channel-   138 Lancet end-   140 Lancet body-   141 Coupling elements-   142 Metal disk-   144 Holding element-   145 Positioning openings-   146 Connecting elements-   147 Tapered portions-   148 Second component-   150 Depressions-   152 Ribs-   154 Transfer openings-   156 Housing-   158 Test chemical-   160 Test chemical field-   162 Chemical ring-   164 Carrier-   166 Seal-   168 Region facing the chambers-   170 Test fields

1-16. (canceled)
 17. A method for producing an analytical magazine,wherein the analytical magazine is designed to receive a plurality ofanalytical aids in a plurality of chambers, wherein the method comprisesthe following steps: providing at least one first component of theanalytical magazine, wherein the first component comprises a pluralityof receptacles, providing a plurality of analytical aids, wherein theanalytical aids are connected to one another and preferably orientedwith respect to one another by means of at least one holding element,introducing the analytical aids into the receptacles, wherein aplurality or preferably all of the chambers are loaded simultaneously;and separating the analytical aids from the holding element, wherein theanalytical aids are produced at least in part integrally with theholding element, wherein the analytical aids comprise lancets and/ormicro-samplers, which are worked from a basic material of the holdingelement, such that the holding element and the analytical aids or partsthereof are produced, wherein the basic material is a metallic basicmaterial.
 18. The method according to claim 17, wherein the holdingelement has at least one metal disk.
 19. The method according to claim17, wherein, prior to separating the analytical aids from the holdingelement, at least one connection to at least one desired breakinglocation is provided between the analytical aids and the holdingelement.
 20. The method according to claim 17, wherein the chambersand/or the analytical aids are configured in such a way that theanalytical aids are mounted such that they are movable wholly or in partfor a sampling movement.
 21. The method according to claim 17,furthermore comprising the following method step: applying at least onesecond component of the analytical magazine to the first component. 22.The method according to claim 17, furthermore comprising the followingmethod step: applying at least one test chemical, wherein the testchemical is designed to change at least one measurable property in thepresence of at least one analyte to be detected, wherein the process ofapplying is effected in such a way that in each case at least one regionof the test chemical faces the interiors of the chambers and isaccessible from inside the chambers.
 23. The method according to claim22, wherein the at least one test chemical is applied in the form of atleast one test chemical field, wherein the test chemical field isapplied to a continuous carrier, wherein the test chemical fieldprovides the regions of the test chemical for a plurality of chambers.24. The method according to claim 23, wherein the test chemical field iscovered with the test chemical throughout.
 25. An analytical magazine,made according to the method of claim 17, comprising a plurality ofanalytical aids received in chambers, wherein the analytical magazinehas at least one test chemical which is designed to change at least onemeasurable property in the presence of at least one analyte to bedetected, wherein the at least one test chemical is applied to acontinuous carrier and forms at least one test chemical field, whereinthe test chemical field is an area coated with test chemical throughoutand is provided jointly for a plurality or preferably all of thechambers, wherein in each case at least one region of the test chemicalfield faces the interiors of the chambers and is accessible from insidethe chambers.
 26. The analytical magazine according to claim 25, whereinthe test chemical field is part of a housing of the analytical magazine.27. An analytical magazine made according to the method of claim 17,comprising a plurality of analytical aids, wherein the analyticalmagazine has at least two chambers in which the analytical aids can bereceived, wherein the analytical aids are received in at least one ofthe chambers, wherein the analytical aids each comprise at least onetest element with at least one test chemical for detecting at least oneanalyte in a liquid sample, wherein the test chemical is at leastsubstantially stable with respect to ambient influences, wherein theanalytical magazine has a housing with at least two components, whereinthe at least two components are connected to one another by a laserwelding method, wherein a first of the at least two components and asecond of the at least two components have a different transparency,wherein at least one first component of the at least two components isconfigured as a substantially rigid component.
 28. The analyticalmagazine made according to the method of claim 17, wherein theanalytical magazine has a housing, wherein the housing comprises amaterial selected from the following materials: a polycarbonate; anacrylonitrile-butadiene-styrene; a cycloolefin copolymer; a polymethylmethacrylate; a polystyrene; and a polyethylene terephthalate.
 29. Theanalytical magazine according to claim 25, wherein the analytical aidsfurthermore have at least one lancet with at least one capillary channelfor receiving body fluid, which is conducted to the test element via thelancet.
 30. The analytical magazine according to claim 29, wherein thecapillary channel of the needle element is coated in order to enableimproved transport of the body fluid.
 31. A method for producing ananalytical magazine, wherein the analytical magazine is designed toreceive a plurality of analytical aids in a plurality of chambers,wherein the analytical aids each have a test chemical, wherein aplurality of the analytical aids are introduced into at least one of thechambers, wherein the analytical magazine has a housing with at leasttwo components, wherein a first of the at least two components and asecond of the at least two components have a different transparency,wherein the at least two components are connected to one another by alaser welding method before or after the analytical aids are introducedinto the chamber.
 32. The method according to claim 31, wherein theanalytical aids additionally each have at least one lancet, wherein theanalytical magazine is sterilized using ionizing radiation after thelaser welding method has been carried out.